RING E3 mechanism for ubiquitin ligation to a disordered substrate visualized for human anaphase-promoting complex

Brown, Nicholas G.; VanderLinden, Ryan; Watson, Edmond R.; Qiao, Renping; Grace, Christy R. R.; Yamaguchi, Masaya; Weissmann, Florian; Frye, Jeremiah J.; Dube, Prakash; Ei Cho, Shein; Actis, Marcelo L.; Rodrigues, Patrick; Fujii, Naoaki; Peters, Jan-Michael; Stark, Holger; Schulman, Brenda A.

doi:10.1073/pnas.1504161112

Title: RING E3 mechanism for ubiquitin ligation to a disordered substrate visualized for human anaphase-promoting complex

Abstract

For many E3 ligases, a mobile RING (Really Interesting New Gene) domain stimulates ubiquitin (Ub) transfer from a thioester-linked E2~Ub intermediate to a lysine on a remotely bound disordered substrate. One such E3 is the gigantic, multisubunit 1.2-MDa anaphase-promoting complex/cyclosome (APC), which controls cell division by ubiquitinating cell cycle regulators to drive their timely degradation. Intrinsically disordered substrates are typically recruited via their KEN-box, D-box, and/or other motifs binding to APC and a coactivator such as CDH1. On the opposite side of the APC, the dynamic catalytic core contains the cullin-like subunit APC2 and its RING partner APC11, which collaborates with the E2 UBCH10 (UBE2C) to ubiquitinate substrates. However, how dynamic RING–E2~Ub catalytic modules such as APC11–UBCH10~Ub collide with distally tethered disordered substrates remains poorly understood. In this paper, we report structural mechanisms of UBCH10 recruitment to APC^CDH1 and substrate ubiquitination. Unexpectedly, in addition to binding APC11’s RING, UBCH10 is corecruited via interactions with APC2, which we visualized in a trapped complex representing an APC^CDH1–UBCH10~Ub–substrate intermediate by cryo-electron microscopy, and in isolation by X-ray crystallography. To our knowledge, this is the first structural view of APC, or any cullin–RING E3, with E2 and substrate juxtaposed, and it reveals how tripartitemore »« less

Authors:

Brown, Nicholas G. ^[1]; VanderLinden, Ryan ^[2]; Watson, Edmond R. ^[3]; Qiao, Renping ^[4]; Grace, Christy R. R. ^[1]; Yamaguchi, Masaya ^[1]; Weissmann, Florian ^[4]; Frye, Jeremiah J. ^[1]; Dube, Prakash ^[5]; Ei Cho, Shein ^[1]; Actis, Marcelo L. ^[6]; Rodrigues, Patrick ^[7]; Fujii, Naoaki ^[6]; Peters, Jan-Michael ^[4]; Stark, Holger ^[5]; Schulman, Brenda A. ^[8]

St. Jude Children's Research Hospital, Memphis, TN (United States). Dept. of Structural Biology
St. Jude Children's Research Hospital, Memphis, TN (United States). Dept. of Structural Biology. Howard Hughes Medical Inst.
St. Jude Children's Research Hospital, Memphis, TN (United States). Dept. of Structural Biology; Univ. of Tennessee Health Sciences Center, Memphis, TN (United States). Dept. of Microbiology, Immunology, and Biochemistry
Vienna Biocenter (VBC) (Austria). Research Inst. of Molecular Pathology (IMP)
Max Planck Inst. for Biophysical Chemistry, Gottingen (Germany); Univ. of Gottingen (Germany). Dept. of 3D Electron Cryomicroscopy. Inst. of Microbiology and Genetics
St. Jude Children's Research Hospital, Memphis, TN (United States). Dept. of Chemical Biology and Therapeutics
St. Jude Children's Research Hospital, Memphis, TN (United States). Hartwell Center for Bioinformatics and Biotechnology
St. Jude Children's Research Hospital, Memphis, TN (United States). Dept. of Structural Biology. Howard Hughes Medical Inst.; Univ. of Tennessee Health Sciences Center, Memphis, TN (United States). Dept. of Microbiology, Immunology, and Biochemistry

Publication Date:: Mon Mar 30 00:00:00 EDT 2015

Research Org.:: Argonne National Laboratory (ANL), Argonne, IL (United States); St. Jude Children's Research Hospital, Memphis, TN (United States); Vienna Biocenter (VBC) (Austria); Max Planck Inst. for Biophysical Chemistry, Gottingen (Germany); Univ. of Goettingen (Germany)

Sponsoring Org.:: USDOE Office of Science (SC); National Inst. of Health (NIH) (United States); Jane Coffin Childs Foundation (United States); American Cancer Society (United States); American Lebanese Syrian Associated Charities (ALSAC) (United States); Howard Hughes Medical Inst. (United States); Japan Society for the Promotion of Science (Japan); Boehringer Ingelheim (Germany); Laura Bassi Centre for Optimized Structural Studies (Austria); European Union (Belgium); Austrian Research Fund (Austria); German Research Foundation (DFG)

OSTI Identifier:: 1197027

Grant/Contract Number:: AC02-06CH11357; R37GM065930; P30CA021765; P41 GM103403; RSG CDD-120969; 227764 MitoSys; Sonderforschungsbereich 860

Resource Type:: Journal Article: Accepted Manuscript

Journal Name:: Proceedings of the National Academy of Sciences of the United States of America

Additional Journal Information:: Journal Volume: 112; Journal Issue: 17; Journal ID: ISSN 0027-8424

Publisher:: National Academy of Sciences

Country of Publication:: United States

Language:: ENGLISH

Subject:: 60 APPLIED LIFE SCIENCES; ubiquitin; anaphase-promoting complex; cullin; E3; electron microscopy

Citation Formats


                    Brown, Nicholas G., VanderLinden, Ryan, Watson, Edmond R., Qiao, Renping, Grace, Christy R. R., Yamaguchi, Masaya, Weissmann, Florian, Frye, Jeremiah J., Dube, Prakash, Ei Cho, Shein, Actis, Marcelo L., Rodrigues, Patrick, Fujii, Naoaki, Peters, Jan-Michael, Stark, Holger, and Schulman, Brenda A. RING E3 mechanism for ubiquitin ligation to a disordered substrate visualized for human anaphase-promoting complex.  United States: N. p., 2015. 
        Web.  doi:10.1073/pnas.1504161112.

Copy to clipboard


                    Brown, Nicholas G., VanderLinden, Ryan, Watson, Edmond R., Qiao, Renping, Grace, Christy R. R., Yamaguchi, Masaya, Weissmann, Florian, Frye, Jeremiah J., Dube, Prakash, Ei Cho, Shein, Actis, Marcelo L., Rodrigues, Patrick, Fujii, Naoaki, Peters, Jan-Michael, Stark, Holger, & Schulman, Brenda A. RING E3 mechanism for ubiquitin ligation to a disordered substrate visualized for human anaphase-promoting complex.  United States.  https://doi.org/10.1073/pnas.1504161112

Copy to clipboard


                    Brown, Nicholas G., VanderLinden, Ryan, Watson, Edmond R., Qiao, Renping, Grace, Christy R. R., Yamaguchi, Masaya, Weissmann, Florian, Frye, Jeremiah J., Dube, Prakash, Ei Cho, Shein, Actis, Marcelo L., Rodrigues, Patrick, Fujii, Naoaki, Peters, Jan-Michael, Stark, Holger, and Schulman, Brenda A. 2015.  
        "RING E3 mechanism for ubiquitin ligation to a disordered substrate visualized for human anaphase-promoting complex".  United States.  https://doi.org/10.1073/pnas.1504161112.  https://www.osti.gov/servlets/purl/1197027.

Copy to clipboard


                    
@article{osti_1197027,

  title        = {RING E3 mechanism for ubiquitin ligation to a disordered substrate visualized for human anaphase-promoting complex},

  author       = {Brown, Nicholas G. and VanderLinden, Ryan and Watson, Edmond R. and Qiao, Renping and Grace, Christy R. R. and Yamaguchi, Masaya and Weissmann, Florian and Frye, Jeremiah J. and Dube, Prakash and Ei Cho, Shein and Actis, Marcelo L. and Rodrigues, Patrick and Fujii, Naoaki and Peters, Jan-Michael and Stark, Holger and Schulman, Brenda A.},

  abstractNote = {For many E3 ligases, a mobile RING (Really Interesting New Gene) domain stimulates ubiquitin (Ub) transfer from a thioester-linked E2~Ub intermediate to a lysine on a remotely bound disordered substrate. One such E3 is the gigantic, multisubunit 1.2-MDa anaphase-promoting complex/cyclosome (APC), which controls cell division by ubiquitinating cell cycle regulators to drive their timely degradation. Intrinsically disordered substrates are typically recruited via their KEN-box, D-box, and/or other motifs binding to APC and a coactivator such as CDH1. On the opposite side of the APC, the dynamic catalytic core contains the cullin-like subunit APC2 and its RING partner APC11, which collaborates with the E2 UBCH10 (UBE2C) to ubiquitinate substrates. However, how dynamic RING–E2~Ub catalytic modules such as APC11–UBCH10~Ub collide with distally tethered disordered substrates remains poorly understood. In this paper, we report structural mechanisms of UBCH10 recruitment to APCCDH1 and substrate ubiquitination. Unexpectedly, in addition to binding APC11’s RING, UBCH10 is corecruited via interactions with APC2, which we visualized in a trapped complex representing an APCCDH1–UBCH10~Ub–substrate intermediate by cryo-electron microscopy, and in isolation by X-ray crystallography. To our knowledge, this is the first structural view of APC, or any cullin–RING E3, with E2 and substrate juxtaposed, and it reveals how tripartite cullin–RING–E2 interactions establish APC’s specificity for UBCH10 and harness a flexible catalytic module to drive ubiquitination of lysines within an accessible zone. Finally, we propose that multisite interactions reduce the degrees of freedom available to dynamic RING E3–E2~Ub catalytic modules, condense the search radius for target lysines, increase the chance of active-site collision with conformationally fluctuating substrates, and enable regulation.},

  doi          = {10.1073/pnas.1504161112},

  url          = {https://www.osti.gov/biblio/1197027},
  journal      = {Proceedings of the National Academy of Sciences of the United States of America},

  issn         = {0027-8424},

  number       = 17,

  volume       = 112,

  place        = {United States},

  year         = {Mon Mar 30 00:00:00 EDT 2015},

  month        = {Mon Mar 30 00:00:00 EDT 2015}

}

Copy to clipboard

Journal Article:

Free Publicly Available Full Text

Accepted Manuscript (DOE)

Publisher's Version of Record

https://doi.org/10.1073/pnas.1504161112

Other availability

Search WorldCat to find libraries that may hold this journal

Citation Metrics:

Cited by: 68 works

Citation information provided by
Web of Science

Save / Share:

Export Metadata

Save to My Library

Works referenced in this record:

Structures of APC/CCdh1 with substrates identify Cdh1 and Apc10 as the D-box co-receptor
journal, November 2010

da Fonseca, Paula C. A.; Kong, Eric H.; Zhang, Ziguo
Nature, Vol. 470, Issue 7333
https://doi.org/10.1038/nature09625

E3 ligase Rad18 promotes monoubiquitination rather than ubiquitin chain formation by E2 enzyme Rad6
journal, March 2011

Hibbert, R. G.; Huang, A.; Boelens, R.
Proceedings of the National Academy of Sciences, Vol. 108, Issue 14
https://doi.org/10.1073/pnas.1017516108

Structure of a RING E3 Trapped in Action Reveals Ligation Mechanism for the Ubiquitin-like Protein NEDD8
journal, June 2014

Scott, Daniel C.; Sviderskiy, Vladislav O.; Monda, Julie K.
Cell, Vol. 157, Issue 7
https://doi.org/10.1016/j.cell.2014.04.037

Activation of UbcH5c∼Ub Is the Result of a Shift in Interdomain Motions of the Conjugate Bound to U-Box E3 Ligase E4B
journal, April 2013

Soss, Sarah E.; Klevit, Rachel E.; Chazin, Walter J.
Biochemistry, Vol. 52, Issue 17
https://doi.org/10.1021/bi3015949

Identification of a physiological E2 module for the human anaphase-promoting complex
journal, October 2009

Williamson, A.; Wickliffe, K. E.; Mellone, B. G.
Proceedings of the National Academy of Sciences, Vol. 106, Issue 43
https://doi.org/10.1073/pnas.0907887106

The zinc-binding region (ZBR) fragment of Emi2 can inhibit APC/C by targeting its association with the coactivator Cdc20 and UBE2C-mediated ubiquitylation
journal, January 2014

Shoji, Shisako; Muto, Yutaka; Ikeda, Mariko
FEBS Open Bio, Vol. 4, Issue 1
https://doi.org/10.1016/j.fob.2014.06.010

A Structurally Unique E2-Binding Domain Activates Ubiquitination by the ERAD E2, Ubc7p, through Multiple Mechanisms
journal, May 2013

Metzger, Meredith B.; Liang, Yu-He; Das, Ranabir
Molecular Cell, Vol. 50, Issue 4
https://doi.org/10.1016/j.molcel.2013.04.004

Identification of a novel ubiquitin-conjugating enzyme involved in mitotic cyclin degradation
journal, April 1996

Yu, Hongtao; King, Randall W.; Peters, Jan-Michael
Current Biology, Vol. 6, Issue 4
https://doi.org/10.1016/S0960-9822(02)00513-4

Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome
journal, October 2014

McGinty, Robert K.; Henrici, Ryan C.; Tan, Song
Nature, Vol. 514, Issue 7524
https://doi.org/10.1038/nature13890

Sequential E2s Drive Polyubiquitin Chain Assembly on APC Targets
journal, July 2007

Rodrigo-Brenni, Monica C.; Morgan, David O.
Cell, Vol. 130, Issue 1
https://doi.org/10.1016/j.cell.2007.05.027

The WD40 Propeller Domain of Cdh1 Functions as a Destruction Box Receptor for APC/C Substrates
journal, May 2005

Kraft, Claudine; Vodermaier, Hartmut C.; Maurer-Stroh, Sebastian
Molecular Cell, Vol. 18, Issue 5
https://doi.org/10.1016/j.molcel.2005.04.023

Mechanism of ubiquitin ligation and lysine prioritization by a HECT E3
journal, August 2013

Kamadurai, Hari B.; Qiu, Yu; Deng, Alan
eLife, Vol. 2
https://doi.org/10.7554/eLife.00828

Ubiquitin Chain Elongation Requires E3-Dependent Tracking of the Emerging Conjugate
journal, October 2014

Kelly, Aileen; Wickliffe, Katherine E.; Song, Ling
Molecular Cell, Vol. 56, Issue 2
https://doi.org/10.1016/j.molcel.2014.09.010

BIRC7–E2 ubiquitin conjugate structure reveals the mechanism of ubiquitin transfer by a RING dimer
journal, August 2012

Dou, Hao; Buetow, Lori; Sibbet, Gary J.
Nature Structural & Molecular Biology, Vol. 19, Issue 9
https://doi.org/10.1038/nsmb.2379

APC15 mediates CDC20 autoubiquitylation by APC/CMCC and disassembly of the mitotic checkpoint complex
journal, September 2012

Uzunova, Kristina; Dye, Billy T.; Schutz, Hannelore
Nature Structural & Molecular Biology, Vol. 19, Issue 11
https://doi.org/10.1038/nsmb.2412

Structure of an APC3–APC16 Complex: Insights into Assembly of the Anaphase-Promoting Complex/Cyclosome
journal, April 2015

Yamaguchi, Masaya; Yu, Shanshan; Qiao, Renping
Journal of Molecular Biology, Vol. 427, Issue 8
https://doi.org/10.1016/j.jmb.2014.11.020

Mechanism of Polyubiquitination by Human Anaphase-Promoting Complex: RING Repurposing for Ubiquitin Chain Assembly
journal, October 2014

Brown, Nicholas G.; Watson, Edmond R.; Weissmann, Florian
Molecular Cell, Vol. 56, Issue 2
https://doi.org/10.1016/j.molcel.2014.09.009

Structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complex
journal, April 2002

Zheng, Ning; Schulman, Brenda A.; Song, Langzhou
Nature, Vol. 416, Issue 6882
https://doi.org/10.1038/416703a

UCSF Chimera?A visualization system for exploratory research and analysis
journal, January 2004

Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C.
Journal of Computational Chemistry, Vol. 25, Issue 13
https://doi.org/10.1002/jcc.20084

Activation of the APC/C Ubiquitin Ligase by Enhanced E2 Efficiency
journal, July 2014

Van Voorhis, Vanessa A.; Morgan, David O.
Current Biology, Vol. 24, Issue 13
https://doi.org/10.1016/j.cub.2014.05.052

Structural Insights into NEDD8 Activation of Cullin-RING Ligases: Conformational Control of Conjugation
journal, September 2008

Duda, David M.; Borg, Laura A.; Scott, Daniel C.
Cell, Vol. 134, Issue 6
https://doi.org/10.1016/j.cell.2008.07.022

Autonomous regulation of the anaphase-promoting complex couples mitosis to S-phase entry
journal, November 2004

Rape, Michael; Kirschner, Marc W.
Nature, Vol. 432, Issue 7017
https://doi.org/10.1038/nature03023

Structural regulation of cullin-RING ubiquitin ligase complexes
journal, April 2011

Duda, David M.; Scott, Daniel C.; Calabrese, Matthew F.
Current Opinion in Structural Biology, Vol. 21, Issue 2
https://doi.org/10.1016/j.sbi.2011.01.003

The Unique N Terminus of the UbcH10 E2 Enzyme Controls the Threshold for APC Activation and Enhances Checkpoint Regulation of the APC
journal, August 2008

Summers, Matthew K.; Pan, Borlan; Mukhyala, Kiran
Molecular Cell, Vol. 31, Issue 4
https://doi.org/10.1016/j.molcel.2008.07.014

Insights into E3 ligase activity revealed by a SUMO–RanGAP1–Ubc9–Nup358 complex
journal, June 2005

Reverter, David; Lima, Christopher D.
Nature, Vol. 435, Issue 7042
https://doi.org/10.1038/nature03588

Emi1 stably binds and inhibits the anaphase-promoting complex/cyclosome as a pseudosubstrate inhibitor
journal, September 2006

Miller, J. J.
Genes & Development, Vol. 20, Issue 17
https://doi.org/10.1101/gad.1454006

Emi1 preferentially inhibits ubiquitin chain elongation by the anaphase-promoting complex
journal, May 2013

Wang, Weiping; Kirschner, Marc W.
Nature Cell Biology, Vol. 15, Issue 7
https://doi.org/10.1038/ncb2755

Identification of a Cullin Homology Region in a Subunit of the Anaphase-Promoting Complex
journal, February 1998

Yu, H.
Science, Vol. 279, Issue 5354
https://doi.org/10.1126/science.279.5354.1219

Mass Spectrometric Analysis of the Anaphase-Promoting Complex from Yeast: Identification of a Subunit Related to Cullins
journal, February 1998

Zachariae, W.
Science, Vol. 279, Issue 5354
https://doi.org/10.1126/science.279.5354.1216

Molecular architecture and mechanism of the anaphase-promoting complex
journal, July 2014

Chang, Leifu; Zhang, Ziguo; Yang, Jing
Nature, Vol. 513, Issue 7518
https://doi.org/10.1038/nature13543

UBE2S elongates ubiquitin chains on APC/C substrates to promote mitotic exit
journal, October 2009

Garnett, Mathew J.; Mansfeld, Jörg; Godwin, Colin
Nature Cell Biology, Vol. 11, Issue 11
https://doi.org/10.1038/ncb1983

A Role for the Fizzy/Cdc20 Family of Proteins in Activation of the APC/C Distinct from Substrate Recruitment
journal, November 2008

Kimata, Yuu; Baxter, Joanne E.; Fry, Andrew M.
Molecular Cell, Vol. 32, Issue 4
https://doi.org/10.1016/j.molcel.2008.09.023

A 20s complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B
journal, April 1995

King, Randall W.; Peters, Jan-Michael; Tugendreich, Stuart
Cell, Vol. 81, Issue 2
https://doi.org/10.1016/0092-8674(95)90338-0

Regulation of Ubiquitin Chain Initiation to Control the Timing of Substrate Degradation
journal, June 2011

Williamson, Adam; Banerjee, Sudeep; Zhu, Xining
Molecular Cell, Vol. 42, Issue 6
https://doi.org/10.1016/j.molcel.2011.04.022

Features and development of Coot
journal, March 2010

Emsley, P.; Lohkamp, B.; Scott, W. G.
Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
https://doi.org/10.1107/S0907444910007493

Substrate binding on the APC/C occurs between the coactivator Cdh1 and the processivity factor Doc1
journal, December 2010

Buschhorn, Bettina A.; Petzold, Georg; Galova, Marta
Nature Structural & Molecular Biology, Vol. 18, Issue 1
https://doi.org/10.1038/nsmb.1979

UBE2S drives elongation of K11-linked ubiquitin chains by the Anaphase-Promoting Complex
journal, January 2010

Wu, T.; Merbl, Y.; Huo, Y.
Proceedings of the National Academy of Sciences, Vol. 107, Issue 4
https://doi.org/10.1073/pnas.0912802107

Insights into Degron Recognition by APC/C Coactivators from the Structure of an Acm1-Cdh1 Complex
journal, June 2013

He, Jun; Chao, William C. H.; Zhang, Ziguo
Molecular Cell, Vol. 50, Issue 5
https://doi.org/10.1016/j.molcel.2013.04.024

Structural and Functional Analysis of the Human Mitotic-specific Ubiquitin-conjugating Enzyme, UbcH10
journal, April 2002

Lin, Yaqiong; Hwang, William C.; Basavappa, Ravi
Journal of Biological Chemistry, Vol. 277, Issue 24
https://doi.org/10.1074/jbc.M109398200

Structural analysis of human Cdc20 supports multisite degron recognition by APC/C
journal, October 2012

Tian, W.; Li, B.; Warrington, R.
Proceedings of the National Academy of Sciences, Vol. 109, Issue 45
https://doi.org/10.1073/pnas.1213438109

APC/C-mediated multiple monoubiquitylation provides an alternative degradation signal for cyclin B1
journal, January 2012

Dimova, Nevena V.; Hathaway, Nathaniel A.; Lee, Byung-Hoon
Nature Cell Biology, Vol. 14, Issue 2
https://doi.org/10.1038/ncb2425

The Processivity of Multiubiquitination by the APC Determines the Order of Substrate Degradation
journal, January 2006

Rape, Michael; Reddy, Sashank K.; Kirschner, Marc W.
Cell, Vol. 124, Issue 1
https://doi.org/10.1016/j.cell.2005.10.032

Structure of an E3:E2∼Ub Complex Reveals an Allosteric Mechanism Shared among RING/U-box Ligases
journal, September 2012

Pruneda, Jonathan N.; Littlefield, Peter J.; Soss, Sarah E.
Molecular Cell, Vol. 47, Issue 6
https://doi.org/10.1016/j.molcel.2012.07.001

Mms2–Ubc13 covalently bound to ubiquitin reveals the structural basis of linkage-specific polyubiquitin chain formation
journal, September 2006

Eddins, Michael J.; Carlile, Candice M.; Gomez, Kamila M.
Nature Structural & Molecular Biology, Vol. 13, Issue 10
https://doi.org/10.1038/nsmb1148

The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis.
journal, February 1995

Sudakin, V.; Ganoth, D.; Dahan, A.
Molecular Biology of the Cell, Vol. 6, Issue 2
https://doi.org/10.1091/mbc.6.2.185

E2-C, a cyclin-selective ubiquitin carrier protein required for the destruction of mitotic cyclins.
journal, April 1996

Aristarkhov, A.; Eytan, E.; Moghe, A.
Proceedings of the National Academy of Sciences, Vol. 93, Issue 9
https://doi.org/10.1073/pnas.93.9.4294

D box and KEN box motifs in budding yeast Hsl1p are required for APC-mediated degradation and direct binding to Cdc20p and Cdh1p
journal, September 2001

Burton, J. L.
Genes & Development, Vol. 15, Issue 18
https://doi.org/10.1101/gad.917901

Electron microscopy structure of human APC/CCDH1–EMI1 reveals multimodal mechanism of E3 ligase shutdown
journal, May 2013

Frye, Jeremiah J.; Brown, Nicholas G.; Petzold, Georg
Nature Structural & Molecular Biology, Vol. 20, Issue 7
https://doi.org/10.1038/nsmb.2593

Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis
journal, July 2012

Plechanovová, Anna; Jaffray, Ellis G.; Tatham, Michael H.
Nature, Vol. 489, Issue 7414
https://doi.org/10.1038/nature11376

Localization of the Coactivator Cdh1 and the Cullin Subunit Apc2 in a Cryo-Electron Microscopy Model of Vertebrate APC/C
journal, December 2005

Dube, Prakash; Herzog, Franz; Gieffers, Christian
Molecular Cell, Vol. 20, Issue 6
https://doi.org/10.1016/j.molcel.2005.11.008

Allosteric Activation of E2-RING Finger-Mediated Ubiquitylation by a Structurally Defined Specific E2-Binding Region of gp78
journal, June 2009

Das, Ranabir; Mariano, Jennifer; Tsai, Yien Che
Molecular Cell, Vol. 34, Issue 6
https://doi.org/10.1016/j.molcel.2009.05.010

Identification of conjugation specificity determinants unmasks vestigial preference for ubiquitin within the NEDD8 E2
journal, February 2008

Huang, Danny T.; Zhuang, Min; Ayrault, Olivier
Nature Structural & Molecular Biology, Vol. 15, Issue 3
https://doi.org/10.1038/nsmb.1387

Structural assembly of cullin-RING ubiquitin ligase complexes
journal, December 2010

Zimmerman, Erik S.; Schulman, Brenda A.; Zheng, Ning
Current Opinion in Structural Biology, Vol. 20, Issue 6
https://doi.org/10.1016/j.sbi.2010.08.010

A UbcH5/Ubiquitin Noncovalent Complex Is Required for Processive BRCA1-Directed Ubiquitination
journal, March 2006

Brzovic, Peter S.; Lissounov, Alexei; Christensen, Devin E.
Molecular Cell, Vol. 21, Issue 6
https://doi.org/10.1016/j.molcel.2006.02.008

Rapid E2-E3 Assembly and Disassembly Enable Processive Ubiquitylation of Cullin-RING Ubiquitin Ligase Substrates
journal, November 2009

Kleiger, Gary; Saha, Anjanabha; Lewis, Steven
Cell, Vol. 139, Issue 5
https://doi.org/10.1016/j.cell.2009.10.030

APC2 Cullin Protein and APC11 RING Protein Comprise the Minimal Ubiquitin Ligase Module of the Anaphase-promoting Complex
journal, December 2001

Tang, Zhanyun; Li, Bing; Bharadwaj, Rajnish
Molecular Biology of the Cell, Vol. 12, Issue 12
https://doi.org/10.1091/mbc.12.12.3839

The ABBA Motif Binds APC/C Activators and Is Shared by APC/C Substrates and Regulators
journal, February 2015

Di Fiore, Barbara; Davey, Norman E.; Hagting, Anja
Developmental Cell, Vol. 32, Issue 3
https://doi.org/10.1016/j.devcel.2015.01.003

RING Domain E3 Ubiquitin Ligases
journal, June 2009

Deshaies, Raymond J.; Joazeiro, Claudio A. P.
Annual Review of Biochemistry, Vol. 78, Issue 1
https://doi.org/10.1146/annurev.biochem.78.101807.093809

PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome
journal, December 2019

Sharma, Deepti; De Falco, Louis; Padavattan, Sivaraman
Nature Communications, Vol. 10, Issue 1
https://doi.org/10.1038/s41467-019-13641-0

Rapid E2-E3 Assembly and Disassembly Enable Processive Ubiquitylation of Cullin-RING Ubiquitin Ligase Substrates
text, January 2009

Anjanabha, Saha,; J., Deshaies, Raymond; Steven, Lewis,
The University of North Carolina at Chapel Hill University Libraries
https://doi.org/10.17615/7baf-c392

Mechanism of ubiquitin ligation and lysine prioritization by a HECT E3
text, January 2013

A., Schulman, Brenda; Marcelo, Actis,; M., Lewis, Steven
The University of North Carolina at Chapel Hill University Libraries
https://doi.org/10.17615/9m8c-ga12

Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome
text, January 2014

S., Tan,; R. C., Henrici,; R. K., McGinty,
Nature Publishing Group
https://doi.org/10.17615/7gsg-zp30

Works referencing / citing this record:

Specific targeting of the deubiquitinase and E3 ligase families with engineered ubiquitin variants: Gorelik and Sidhu
journal, November 2016

Gorelik, Maryna; Sidhu, Sachdev S.
Bioengineering & Translational Medicine, Vol. 2, Issue 1
https://doi.org/10.1002/btm2.10044

Detection and Analysis of Cell Cycle-Associated APC/C-Mediated Cellular Ubiquitylation In Vitro and In Vivo
book, September 2016

Cedeño, Cesyen; La Monaca, Esther; Esposito, Mara
Methods in Molecular Biology
https://doi.org/10.1007/978-1-4939-3756-1_15

E2 enzymes: more than just middle men
journal, March 2016

Stewart, Mikaela D.; Ritterhoff, Tobias; Klevit, Rachel E.
Cell Research, Vol. 26, Issue 4
https://doi.org/10.1038/cr.2016.35

The increasing complexity of the ubiquitin code
journal, May 2016

Yau, Richard; Rape, Michael
Nature Cell Biology, Vol. 18, Issue 6
https://doi.org/10.1038/ncb3358

Structural insights into the catalysis and regulation of E3 ubiquitin ligases
journal, August 2016

Buetow, Lori; Huang, Danny T.
Nature Reviews Molecular Cell Biology, Vol. 17, Issue 10
https://doi.org/10.1038/nrm.2016.91

Mechanisms and functions of ribosome-associated protein quality control
journal, April 2019

Joazeiro, Claudio A. P.
Nature Reviews Molecular Cell Biology, Vol. 20, Issue 6
https://doi.org/10.1038/s41580-019-0118-2

biGBac enables rapid gene assembly for the expression of large multisubunit protein complexes
journal, April 2016

Weissmann, Florian; Petzold, Georg; VanderLinden, Ryan
Proceedings of the National Academy of Sciences, Vol. 113, Issue 19
https://doi.org/10.1073/pnas.1604935113

Design Principles Involving Protein Disorder Facilitate Specific Substrate Selection and Degradation by the Ubiquitin-Proteasome System
journal, February 2016

Guharoy, Mainak; Bhowmick, Pallab; Tompa, Peter
Journal of Biological Chemistry, Vol. 291, Issue 13
https://doi.org/10.1074/jbc.r115.692665

RETRACTED ARTICLE: Role of oxidative stress in Retinitis pigmentosa: new involved pathways by an RNA-Seq analysis
journal, December 2018

Donato, Luigi; Scimone, Concetta; Nicocia, Giacomo
Cell Cycle, Vol. 18, Issue 1
https://doi.org/10.1080/15384101.2018.1558873

Insights into APC/C: from cellular function to diseases and therapeutics
journal, March 2016

Zhou, Zhuan; He, Mingjing; Shah, Anil A.
Cell Division, Vol. 11, Issue 1
https://doi.org/10.1186/s13008-016-0021-6

Mechanisms for the temporal regulation of substrate ubiquitination by the anaphase-promoting complex/cyclosome
journal, December 2019

Bansal, Shivangee; Tiwari, Swati
Cell Division, Vol. 14, Issue 1
https://doi.org/10.1186/s13008-019-0057-5

Cezanne/ OTUD 7B is a cell cycle‐regulated deubiquitinase that antagonizes the degradation of APC /C substrates
journal, July 2018

Bonacci, Thomas; Suzuki, Aussie; Grant, Gavin D.
The EMBO Journal, Vol. 37, Issue 16
https://doi.org/10.15252/embj.201798701

Enzymatic Logic of Ubiquitin Chain Assembly
journal, July 2019

Deol, Kirandeep K.; Lorenz, Sonja; Strieter, Eric R.
Frontiers in Physiology, Vol. 10
https://doi.org/10.3389/fphys.2019.00835

Sumoylation promotes optimal APC/C activation and timely anaphase
journal, March 2018

Lee, Christine C.; Li, Bing; Yu, Hongtao
eLife, Vol. 7
https://doi.org/10.7554/elife.29539

Molecular basis of APC/C regulation by the spindle assembly checkpoint
journal, August 2016

Alfieri, Claudio; Chang, Leifu; Zhang, Ziguo
Nature, Vol. 536, Issue 7617
https://doi.org/10.1038/nature19083

Mechanism of APC/C ^CDC20 activation by mitotic phosphorylation
journal, April 2016

Qiao, Renping; Weissmann, Florian; Yamaguchi, Masaya
Proceedings of the National Academy of Sciences, Vol. 113, Issue 19
https://doi.org/10.1073/pnas.1604929113

Visualizing the complex functions and mechanisms of the anaphase promoting complex/cyclosome (APC/C)
journal, November 2017

Alfieri, Claudio; Zhang, Suyang; Barford, David
Open Biology, Vol. 7, Issue 11
https://doi.org/10.1098/rsob.170204

Quantifying the heterogeneity of macromolecular machines by mass photometry
journal, April 2020

Sonn-Segev, Adar; Belacic, Katarina; Bodrug, Tatyana
Nature Communications, Vol. 11, Issue 1
https://doi.org/10.1038/s41467-020-15642-w

Atomic-Resolution Structures of the APC/C Subunits Apc4 and the Apc5 N-Terminal Domain
journal, October 2015

Cronin, Nora B.; Yang, Jing; Zhang, Ziguo
Journal of Molecular Biology, Vol. 427, Issue 20
https://doi.org/10.1016/j.jmb.2015.08.023

Structural Basis of BRCC36 Function in DNA Repair and Immune Regulation
journal, August 2019

Rabl, Julius; Bunker, Richard D.; Schenk, Andreas D.
Molecular Cell, Vol. 75, Issue 3
https://doi.org/10.1016/j.molcel.2019.06.002

Ubiquitin-like Protein Conjugation: Structures, Chemistry, and Mechanism
journal, February 2017

Cappadocia, Laurent; Lima, Christopher D.
Chemical Reviews, Vol. 118, Issue 3
https://doi.org/10.1021/acs.chemrev.6b00737

Molecular basis of APC/C regulation by the spindle assembly checkpoint
journal, August 2016

Alfieri, Claudio; Chang, Leifu; Zhang, Ziguo
Nature, Vol. 536, Issue 7617
https://doi.org/10.1038/nature19083

Specificity and disease in the ubiquitin system
journal, February 2016

Chaugule, Viduth K.; Walden, Helen
Biochemical Society Transactions, Vol. 44, Issue 1
https://doi.org/10.1042/bst20150209

Visualizing the complex functions and mechanisms of the anaphase promoting complex/cyclosome (APC/C)
journal, November 2017

Alfieri, Claudio; Zhang, Suyang; Barford, David
Open Biology, Vol. 7, Issue 11
https://doi.org/10.1098/rsob.170204

Insights into APC/C: from cellular function to diseases and therapeutics
journal, March 2016

Zhou, Zhuan; He, Mingjing; Shah, Anil A.
Cell Division, Vol. 11, Issue 1
https://doi.org/10.1186/s13008-016-0021-6

Mechanisms for the temporal regulation of substrate ubiquitination by the anaphase-promoting complex/cyclosome
journal, December 2019

Bansal, Shivangee; Tiwari, Swati
Cell Division, Vol. 14, Issue 1
https://doi.org/10.1186/s13008-019-0057-5

Synergistic inhibition of the APC/C by the removal of APC15 in HCT116 cells lacking UBE2C
journal, September 2016

Garvanska, Dimitriya H.; Larsen, Marie Sofie Yoo; Nilsson, Jakob
Biology Open, Vol. 5, Issue 10
https://doi.org/10.1242/bio.020842

Dual RING E3 Architectures Regulate Multiubiquitination and Ubiquitin Chain Elongation by APC/C
text, January 2016

A., Jarvis, Marc; David, Yanishevski,; G., Brown, Nicholas
The University of North Carolina at Chapel Hill University Libraries
https://doi.org/10.17615/kssb-fk64

The mitotic checkpoint complex (MCC): looking back and forth after 15 years
journal, January 2016

Liu, Song-Tao; Zhang, Hang
AIMS Molecular Science, Vol. 3, Issue 4
https://doi.org/10.3934/molsci.2016.4.597

Similar records in OSTI.GOV collections:

Protein engineering of a ubiquitin-variant inhibitor of APC/C identifies a cryptic K48 ubiquitin chain binding site

Journal Article Watson, Edmond; Grace, Christy; Zhang, Wei; ... - Proceedings of the National Academy of Sciences of the United States of America

Ubiquitin (Ub)-mediated proteolysis is a fundamental mechanism used by eukaryotic cells to maintain homeostasis and protein quality, and to control timing in biological processes. Two essential aspects of Ub regulation are conjugation through E1-E2-E3 enzymatic cascades and recognition by Ub-binding domains. An emerging theme in the Ub field is that these 2 properties are often amalgamated in conjugation enzymes. In addition to covalent thioester linkage to Ub’s C terminus for Ub transfer reactions, conjugation enzymes often bind noncovalently and weakly to Ub at “exosites.” However, identification of such sites is typically empirical and particularly challenging in large molecular machines. Inmore »« less
Cited by 15
https://doi.org/10.1073/pnas.1902889116

Full Text Available
Structure of an APC3–APC16 Complex: Insights into Assembly of the Anaphase-Promoting Complex/Cyclosome

Journal Article Yamaguchi, Masaya; Yu, Shanshan; Qiao, Renping; ... - Journal of Molecular Biology

The anaphase-promoting complex/cyclosome (APC/C) is a massive E3 ligase that controls mitosis by catalyzing ubiquitination of key cell cycle regulatory proteins. The APC/C assembly contains two subcomplexes: the “Platform” centers around a cullin-RING-like E3 ligase catalytic core; the “Arc Lamp” is a hub that mediates transient association with regulators and ubiquitination substrates. The Arc Lamp contains the small subunits APC16, CDC26, and APC13, and tetratricopeptide repeat (TPR) proteins (APC7, APC3, APC6, and APC8) that homodimerize and stack with quasi-2-fold symmetry. Within the APC/C complex, APC3 serves as center for regulation. APC3's TPR motifs recruit substrate-binding coactivators, CDC20 and CDH1, viamore »« less
Cited by 28
https://doi.org/10.1016/j.jmb.2014.11.020

Full Text Available
Mechanism of Polyubiquitination by Human Anaphase-Promoting Complex: RING Repurposing for Ubiquitin Chain Assembly

Journal Article Brown, Nicholas; Watson, Edmond; Weissmann, Florian; ... - Molecular Cell

Polyubiquitination by E2 and E3 enzymes is a predominant mechanism regulating protein function. Some RING E3s, including anaphase-promoting complex/cyclosome (APC), catalyze polyubiquitination by sequential reactions with two different E2s. An initiating E2 ligates ubiquitin to an E3-bound substrate. Another E2 grows a polyubiquitin chain on the ubiquitin-primed substrate through poorly defined mechanisms. Here in this paper we show that human APC’s RING domain is repurposed for dual functions in polyubiquitination. The canonical RING surface activates an initiating E2-ubiquitin intermediate for substrate modification. However, APC engages and activates its specialized ubiquitin chain-elongating E2 UBE2S in ways that differ from current paradigms.more »« less
Cited by 78
https://doi.org/10.1016/j.molcel.2014.09.009
Structural Insights into NEDD8 Activation of Cullin-RING Ligases: Conformational Control of Conjugation

Journal Article Duda, D; Borg, L; Scott, D; ... - Cell

Cullin-RING ligases (CRLs) comprise the largest ubiquitin E3 subclass, in which a central cullin subunit links a substrate-binding adaptor with an E2-binding RING. Covalent attachment of the ubiquitin-like protein NEDD8 to a conserved C-terminal domain (ctd) lysine stimulates CRL ubiquitination activity and prevents binding of the inhibitor CAND1. Here we report striking conformational rearrangements in the crystal structure of NEDD8{approx}Cul5ctd-Rbx1 and SAXS analysis of NEDD8{approx}Cul1ctd-Rbx1 relative to their unmodified counterparts. In NEDD8ylated CRL structures, the cullin WHB and Rbx1 RING subdomains are dramatically reoriented, eliminating a CAND1-binding site and imparting multiple potential catalytic geometries to an associated E2. Biochemical analysesmore »« less
https://doi.org/10.1016/j.cell.2008.07.022
An Allosteric Inhibitor of the Human Cdc34 Ubiquitin-Conjugating Enzyme

Journal Article Ceccarelli, Derek; Tang, Xiaojing; Pelletier, Benoit; ... - Cell

In the ubiquitin-proteasome system (UPS), E2 enzymes mediate the conjugation of ubiquitin to substrates and thereby control protein stability and interactions. The E2 enzyme hCdc34 catalyzes the ubiquitination of hundreds of proteins in conjunction with the cullin-RING (CRL) superfamily of E3 enzymes. We identified a small molecule termed CC0651 that selectively inhibits hCdc34. Structure determination revealed that CC0651 inserts into a cryptic binding pocket on hCdc34 distant from the catalytic site, causing subtle but wholesale displacement of E2 secondary structural elements. CC0651 analogs inhibited proliferation of human cancer cell lines and caused accumulation of the SCF{sup Skp2} substrate p27{sup Kip1}.more »« less
https://doi.org/10.1016/j.cell.2011.05.039

Similar Records

Title: RING E3 mechanism for ubiquitin ligation to a disordered substrate visualized for human anaphase-promoting complex

Abstract

Citation Formats

Structures of APC/CCdh1 with substrates identify Cdh1 and Apc10 as the D-box co-receptor journal, November 2010

E3 ligase Rad18 promotes monoubiquitination rather than ubiquitin chain formation by E2 enzyme Rad6 journal, March 2011

Structure of a RING E3 Trapped in Action Reveals Ligation Mechanism for the Ubiquitin-like Protein NEDD8 journal, June 2014

Activation of UbcH5c∼Ub Is the Result of a Shift in Interdomain Motions of the Conjugate Bound to U-Box E3 Ligase E4B journal, April 2013

Identification of a physiological E2 module for the human anaphase-promoting complex journal, October 2009

The zinc-binding region (ZBR) fragment of Emi2 can inhibit APC/C by targeting its association with the coactivator Cdc20 and UBE2C-mediated ubiquitylation journal, January 2014

A Structurally Unique E2-Binding Domain Activates Ubiquitination by the ERAD E2, Ubc7p, through Multiple Mechanisms journal, May 2013

Identification of a novel ubiquitin-conjugating enzyme involved in mitotic cyclin degradation journal, April 1996

Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome journal, October 2014

Sequential E2s Drive Polyubiquitin Chain Assembly on APC Targets journal, July 2007

The WD40 Propeller Domain of Cdh1 Functions as a Destruction Box Receptor for APC/C Substrates journal, May 2005

Mechanism of ubiquitin ligation and lysine prioritization by a HECT E3 journal, August 2013

Ubiquitin Chain Elongation Requires E3-Dependent Tracking of the Emerging Conjugate journal, October 2014

BIRC7–E2 ubiquitin conjugate structure reveals the mechanism of ubiquitin transfer by a RING dimer journal, August 2012

APC15 mediates CDC20 autoubiquitylation by APC/CMCC and disassembly of the mitotic checkpoint complex journal, September 2012

Structure of an APC3–APC16 Complex: Insights into Assembly of the Anaphase-Promoting Complex/Cyclosome journal, April 2015

Mechanism of Polyubiquitination by Human Anaphase-Promoting Complex: RING Repurposing for Ubiquitin Chain Assembly journal, October 2014

Structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complex journal, April 2002

UCSF Chimera?A visualization system for exploratory research and analysis journal, January 2004

Activation of the APC/C Ubiquitin Ligase by Enhanced E2 Efficiency journal, July 2014

Structural Insights into NEDD8 Activation of Cullin-RING Ligases: Conformational Control of Conjugation journal, September 2008

Autonomous regulation of the anaphase-promoting complex couples mitosis to S-phase entry journal, November 2004

Structural regulation of cullin-RING ubiquitin ligase complexes journal, April 2011

The Unique N Terminus of the UbcH10 E2 Enzyme Controls the Threshold for APC Activation and Enhances Checkpoint Regulation of the APC journal, August 2008

Insights into E3 ligase activity revealed by a SUMO–RanGAP1–Ubc9–Nup358 complex journal, June 2005

Emi1 stably binds and inhibits the anaphase-promoting complex/cyclosome as a pseudosubstrate inhibitor journal, September 2006

Emi1 preferentially inhibits ubiquitin chain elongation by the anaphase-promoting complex journal, May 2013

Identification of a Cullin Homology Region in a Subunit of the Anaphase-Promoting Complex journal, February 1998

Mass Spectrometric Analysis of the Anaphase-Promoting Complex from Yeast: Identification of a Subunit Related to Cullins journal, February 1998

Molecular architecture and mechanism of the anaphase-promoting complex journal, July 2014

UBE2S elongates ubiquitin chains on APC/C substrates to promote mitotic exit journal, October 2009

A Role for the Fizzy/Cdc20 Family of Proteins in Activation of the APC/C Distinct from Substrate Recruitment journal, November 2008

A 20s complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B journal, April 1995

Regulation of Ubiquitin Chain Initiation to Control the Timing of Substrate Degradation journal, June 2011

Features and development of Coot journal, March 2010

Substrate binding on the APC/C occurs between the coactivator Cdh1 and the processivity factor Doc1 journal, December 2010

UBE2S drives elongation of K11-linked ubiquitin chains by the Anaphase-Promoting Complex journal, January 2010

Insights into Degron Recognition by APC/C Coactivators from the Structure of an Acm1-Cdh1 Complex journal, June 2013

Structural and Functional Analysis of the Human Mitotic-specific Ubiquitin-conjugating Enzyme, UbcH10 journal, April 2002

Structural analysis of human Cdc20 supports multisite degron recognition by APC/C journal, October 2012

APC/C-mediated multiple monoubiquitylation provides an alternative degradation signal for cyclin B1 journal, January 2012

The Processivity of Multiubiquitination by the APC Determines the Order of Substrate Degradation journal, January 2006

Structure of an E3:E2∼Ub Complex Reveals an Allosteric Mechanism Shared among RING/U-box Ligases journal, September 2012

Mms2–Ubc13 covalently bound to ubiquitin reveals the structural basis of linkage-specific polyubiquitin chain formation journal, September 2006

The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis. journal, February 1995

E2-C, a cyclin-selective ubiquitin carrier protein required for the destruction of mitotic cyclins. journal, April 1996

D box and KEN box motifs in budding yeast Hsl1p are required for APC-mediated degradation and direct binding to Cdc20p and Cdh1p journal, September 2001

Electron microscopy structure of human APC/CCDH1–EMI1 reveals multimodal mechanism of E3 ligase shutdown journal, May 2013

Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis journal, July 2012

Localization of the Coactivator Cdh1 and the Cullin Subunit Apc2 in a Cryo-Electron Microscopy Model of Vertebrate APC/C journal, December 2005

Allosteric Activation of E2-RING Finger-Mediated Ubiquitylation by a Structurally Defined Specific E2-Binding Region of gp78 journal, June 2009

Identification of conjugation specificity determinants unmasks vestigial preference for ubiquitin within the NEDD8 E2 journal, February 2008

Structural assembly of cullin-RING ubiquitin ligase complexes journal, December 2010

A UbcH5/Ubiquitin Noncovalent Complex Is Required for Processive BRCA1-Directed Ubiquitination journal, March 2006

Rapid E2-E3 Assembly and Disassembly Enable Processive Ubiquitylation of Cullin-RING Ubiquitin Ligase Substrates journal, November 2009

APC2 Cullin Protein and APC11 RING Protein Comprise the Minimal Ubiquitin Ligase Module of the Anaphase-promoting Complex journal, December 2001

The ABBA Motif Binds APC/C Activators and Is Shared by APC/C Substrates and Regulators journal, February 2015

RING Domain E3 Ubiquitin Ligases journal, June 2009

PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome journal, December 2019

Rapid E2-E3 Assembly and Disassembly Enable Processive Ubiquitylation of Cullin-RING Ubiquitin Ligase Substrates text, January 2009

Mechanism of ubiquitin ligation and lysine prioritization by a HECT E3 text, January 2013

Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome text, January 2014

Specific targeting of the deubiquitinase and E3 ligase families with engineered ubiquitin variants: Gorelik and Sidhu journal, November 2016

Detection and Analysis of Cell Cycle-Associated APC/C-Mediated Cellular Ubiquitylation In Vitro and In Vivo book, September 2016

E2 enzymes: more than just middle men journal, March 2016

The increasing complexity of the ubiquitin code journal, May 2016

Structural insights into the catalysis and regulation of E3 ubiquitin ligases journal, August 2016

Mechanisms and functions of ribosome-associated protein quality control journal, April 2019

biGBac enables rapid gene assembly for the expression of large multisubunit protein complexes journal, April 2016

Design Principles Involving Protein Disorder Facilitate Specific Substrate Selection and Degradation by the Ubiquitin-Proteasome System journal, February 2016

RETRACTED ARTICLE: Role of oxidative stress in Retinitis pigmentosa: new involved pathways by an RNA-Seq analysis journal, December 2018

Insights into APC/C: from cellular function to diseases and therapeutics journal, March 2016

Mechanisms for the temporal regulation of substrate ubiquitination by the anaphase-promoting complex/cyclosome journal, December 2019

Cezanne/ OTUD 7B is a cell cycle‐regulated deubiquitinase that antagonizes the degradation of APC /C substrates journal, July 2018

Enzymatic Logic of Ubiquitin Chain Assembly journal, July 2019

Sumoylation promotes optimal APC/C activation and timely anaphase journal, March 2018

Molecular basis of APC/C regulation by the spindle assembly checkpoint journal, August 2016

Structures of APC/CCdh1 with substrates identify Cdh1 and Apc10 as the D-box co-receptor
journal, November 2010

E3 ligase Rad18 promotes monoubiquitination rather than ubiquitin chain formation by E2 enzyme Rad6
journal, March 2011

Structure of a RING E3 Trapped in Action Reveals Ligation Mechanism for the Ubiquitin-like Protein NEDD8
journal, June 2014

Activation of UbcH5c∼Ub Is the Result of a Shift in Interdomain Motions of the Conjugate Bound to U-Box E3 Ligase E4B
journal, April 2013

Identification of a physiological E2 module for the human anaphase-promoting complex
journal, October 2009

The zinc-binding region (ZBR) fragment of Emi2 can inhibit APC/C by targeting its association with the coactivator Cdc20 and UBE2C-mediated ubiquitylation
journal, January 2014

A Structurally Unique E2-Binding Domain Activates Ubiquitination by the ERAD E2, Ubc7p, through Multiple Mechanisms
journal, May 2013

Identification of a novel ubiquitin-conjugating enzyme involved in mitotic cyclin degradation
journal, April 1996

Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome
journal, October 2014

Sequential E2s Drive Polyubiquitin Chain Assembly on APC Targets
journal, July 2007

The WD40 Propeller Domain of Cdh1 Functions as a Destruction Box Receptor for APC/C Substrates
journal, May 2005

Mechanism of ubiquitin ligation and lysine prioritization by a HECT E3
journal, August 2013

Ubiquitin Chain Elongation Requires E3-Dependent Tracking of the Emerging Conjugate
journal, October 2014

BIRC7–E2 ubiquitin conjugate structure reveals the mechanism of ubiquitin transfer by a RING dimer
journal, August 2012

APC15 mediates CDC20 autoubiquitylation by APC/CMCC and disassembly of the mitotic checkpoint complex
journal, September 2012

Structure of an APC3–APC16 Complex: Insights into Assembly of the Anaphase-Promoting Complex/Cyclosome
journal, April 2015

Mechanism of Polyubiquitination by Human Anaphase-Promoting Complex: RING Repurposing for Ubiquitin Chain Assembly
journal, October 2014

Structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complex
journal, April 2002

UCSF Chimera?A visualization system for exploratory research and analysis
journal, January 2004

Activation of the APC/C Ubiquitin Ligase by Enhanced E2 Efficiency
journal, July 2014

Structural Insights into NEDD8 Activation of Cullin-RING Ligases: Conformational Control of Conjugation
journal, September 2008

Autonomous regulation of the anaphase-promoting complex couples mitosis to S-phase entry
journal, November 2004

Structural regulation of cullin-RING ubiquitin ligase complexes
journal, April 2011

The Unique N Terminus of the UbcH10 E2 Enzyme Controls the Threshold for APC Activation and Enhances Checkpoint Regulation of the APC
journal, August 2008

Insights into E3 ligase activity revealed by a SUMO–RanGAP1–Ubc9–Nup358 complex
journal, June 2005

Emi1 stably binds and inhibits the anaphase-promoting complex/cyclosome as a pseudosubstrate inhibitor
journal, September 2006

Emi1 preferentially inhibits ubiquitin chain elongation by the anaphase-promoting complex
journal, May 2013

Identification of a Cullin Homology Region in a Subunit of the Anaphase-Promoting Complex
journal, February 1998

Mass Spectrometric Analysis of the Anaphase-Promoting Complex from Yeast: Identification of a Subunit Related to Cullins
journal, February 1998

Molecular architecture and mechanism of the anaphase-promoting complex
journal, July 2014

UBE2S elongates ubiquitin chains on APC/C substrates to promote mitotic exit
journal, October 2009

A Role for the Fizzy/Cdc20 Family of Proteins in Activation of the APC/C Distinct from Substrate Recruitment
journal, November 2008

A 20s complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B
journal, April 1995

Regulation of Ubiquitin Chain Initiation to Control the Timing of Substrate Degradation
journal, June 2011

Features and development of Coot
journal, March 2010

Substrate binding on the APC/C occurs between the coactivator Cdh1 and the processivity factor Doc1
journal, December 2010

UBE2S drives elongation of K11-linked ubiquitin chains by the Anaphase-Promoting Complex
journal, January 2010

Insights into Degron Recognition by APC/C Coactivators from the Structure of an Acm1-Cdh1 Complex
journal, June 2013

Structural and Functional Analysis of the Human Mitotic-specific Ubiquitin-conjugating Enzyme, UbcH10
journal, April 2002

Structural analysis of human Cdc20 supports multisite degron recognition by APC/C
journal, October 2012

APC/C-mediated multiple monoubiquitylation provides an alternative degradation signal for cyclin B1
journal, January 2012

The Processivity of Multiubiquitination by the APC Determines the Order of Substrate Degradation
journal, January 2006

Structure of an E3:E2∼Ub Complex Reveals an Allosteric Mechanism Shared among RING/U-box Ligases
journal, September 2012

Mms2–Ubc13 covalently bound to ubiquitin reveals the structural basis of linkage-specific polyubiquitin chain formation
journal, September 2006

The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis.
journal, February 1995

E2-C, a cyclin-selective ubiquitin carrier protein required for the destruction of mitotic cyclins.
journal, April 1996

D box and KEN box motifs in budding yeast Hsl1p are required for APC-mediated degradation and direct binding to Cdc20p and Cdh1p
journal, September 2001

Electron microscopy structure of human APC/CCDH1–EMI1 reveals multimodal mechanism of E3 ligase shutdown
journal, May 2013

Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis
journal, July 2012

Localization of the Coactivator Cdh1 and the Cullin Subunit Apc2 in a Cryo-Electron Microscopy Model of Vertebrate APC/C
journal, December 2005

Allosteric Activation of E2-RING Finger-Mediated Ubiquitylation by a Structurally Defined Specific E2-Binding Region of gp78
journal, June 2009

Identification of conjugation specificity determinants unmasks vestigial preference for ubiquitin within the NEDD8 E2
journal, February 2008

Structural assembly of cullin-RING ubiquitin ligase complexes
journal, December 2010

A UbcH5/Ubiquitin Noncovalent Complex Is Required for Processive BRCA1-Directed Ubiquitination
journal, March 2006

Rapid E2-E3 Assembly and Disassembly Enable Processive Ubiquitylation of Cullin-RING Ubiquitin Ligase Substrates
journal, November 2009

APC2 Cullin Protein and APC11 RING Protein Comprise the Minimal Ubiquitin Ligase Module of the Anaphase-promoting Complex
journal, December 2001

The ABBA Motif Binds APC/C Activators and Is Shared by APC/C Substrates and Regulators
journal, February 2015

RING Domain E3 Ubiquitin Ligases
journal, June 2009

PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome
journal, December 2019

Rapid E2-E3 Assembly and Disassembly Enable Processive Ubiquitylation of Cullin-RING Ubiquitin Ligase Substrates
text, January 2009

Mechanism of ubiquitin ligation and lysine prioritization by a HECT E3
text, January 2013

Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome
text, January 2014

Specific targeting of the deubiquitinase and E3 ligase families with engineered ubiquitin variants: Gorelik and Sidhu
journal, November 2016

Detection and Analysis of Cell Cycle-Associated APC/C-Mediated Cellular Ubiquitylation In Vitro and In Vivo
book, September 2016

E2 enzymes: more than just middle men
journal, March 2016

The increasing complexity of the ubiquitin code
journal, May 2016

Structural insights into the catalysis and regulation of E3 ubiquitin ligases
journal, August 2016

Mechanisms and functions of ribosome-associated protein quality control
journal, April 2019

biGBac enables rapid gene assembly for the expression of large multisubunit protein complexes
journal, April 2016

Design Principles Involving Protein Disorder Facilitate Specific Substrate Selection and Degradation by the Ubiquitin-Proteasome System
journal, February 2016

RETRACTED ARTICLE: Role of oxidative stress in Retinitis pigmentosa: new involved pathways by an RNA-Seq analysis
journal, December 2018

Insights into APC/C: from cellular function to diseases and therapeutics
journal, March 2016

Mechanisms for the temporal regulation of substrate ubiquitination by the anaphase-promoting complex/cyclosome
journal, December 2019

Cezanne/ OTUD 7B is a cell cycle‐regulated deubiquitinase that antagonizes the degradation of APC /C substrates
journal, July 2018

Enzymatic Logic of Ubiquitin Chain Assembly
journal, July 2019

Sumoylation promotes optimal APC/C activation and timely anaphase
journal, March 2018

Molecular basis of APC/C regulation by the spindle assembly checkpoint
journal, August 2016

Mechanism of APC/C ^CDC20 activation by mitotic phosphorylation
journal, April 2016

Visualizing the complex functions and mechanisms of the anaphase promoting complex/cyclosome (APC/C)
journal, November 2017

Quantifying the heterogeneity of macromolecular machines by mass photometry
journal, April 2020