The DDB1–DCAF1–Vpr–UNG2 crystal structure reveals how HIV-1 Vpr steers human UNG2 toward destruction

Wu, Ying; Zhou, Xiaohong; Barnes, Christopher O.; DeLucia, Maria; Cohen, Aina E.; Gronenborn, Angela M.; Ahn, Jinwoo; Calero, Guillermo

doi:10.1038/nsmb.3284

The DDB1–DCAF1–Vpr–UNG2 crystal structure reveals how HIV-1 Vpr steers human UNG2 toward destruction

Journal Article · Mon Aug 29 00:00:00 EDT 2016 · Nature Structural & Molecular Biology

DOI:https://doi.org/10.1038/nsmb.3284· OSTI ID:1330269

Wu, Ying ^[1]; Zhou, Xiaohong ^[1]; Barnes, Christopher O. ^[1]; DeLucia, Maria ^[1]; Cohen, Aina E. ^[2]; Gronenborn, Angela M. ^[1]; Ahn, Jinwoo ^[1]; Calero, Guillermo ^[1]

Univ. of Pittsburgh, PA (United States)
Stanford Univ., Menlo Park, CA (United States)

The HIV-1 accessory protein Vpr is required for efficient viral infection of macrophages and promotion of viral replication in T cells. Vpr's biological activities are closely linked to the interaction with human DCAF1, a cellular substrate receptor of the Cullin4–RING E3 ubiquitin ligase (CRL4) of the host ubiquitin–proteasome-mediated protein degradation pathway. The molecular details of how Vpr usurps the protein degradation pathway have not been delineated. Here we present the crystal structure of the DDB1–DCAF1–HIV-1–Vpr–uracil-DNA glycosylase (UNG2) complex. The structure reveals how Vpr engages with DCAF1, creating a binding interface for UNG2 recruitment in a manner distinct from the recruitment of SAMHD1 by Vpx proteins. Vpr and Vpx use similar N-terminal and helical regions to bind the substrate receptor, whereas different regions target the specific cellular substrates. In conclusion, Vpr uses molecular mimicry of DNA by a variable loop for specific recruitment of the UNG2 substrate.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); National Inst. of Health; National Inst. of General Medical Sciences

Grant/Contract Number:: AC02-76SF00515

OSTI ID:: 1330269

Alternate ID(s):: OSTI ID: 1360205

Journal Information:: Nature Structural & Molecular Biology, Journal Name: Nature Structural & Molecular Biology Journal Issue: 10 Vol. 23; ISSN 1545-9993

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

References (63)

Vpr Is Required for Efficient Replication of Human Immunodeficiency Virus Type-1 in Mononuclear Phagocytes Connor, Ruth I.; Chen, Benjamin Kuan; Choe, Sunny Virology, Vol. 206, Issue 2 https://doi.org/10.1006/viro.1995.1016	journal	February 1995
Complex Evolutionary History of Primate LentiviralvprGenes Tristem, Michael; Purvis, Andy; Quicke, Donald L. J. Virology, Vol. 240, Issue 2 https://doi.org/10.1006/viro.1997.8929	journal	January 1998
Structure and function of WD40 domain proteins Xu, Chao; Min, Jinrong Protein & Cell, Vol. 2, Issue 3 https://doi.org/10.1007/s13238-011-1018-1	journal	March 2011
Crystal structure of human uracil-DNA glycosylase in complex with a protein inhibitor: Protein mimicry of DNA Mol, Clifford D.; Arvai, Andrew S.; Sanderson, Russell J. Cell, Vol. 82, Issue 5 https://doi.org/10.1016/0092-8674(95)90467-0	journal	September 1995
NMR Structure of the HIV-1 Regulatory Protein VPR Morellet, N.; Bouaziz, S.; Petitjean, P. Journal of Molecular Biology, Vol. 327, Issue 1 https://doi.org/10.1016/S0022-2836(03)00060-3	journal	March 2003
Structure of DDB1 in Complex with a Paramyxovirus V Protein: Viral Hijack of a Propeller Cluster in Ubiquitin Ligase Li, Ti; Chen, Xiujuan; Garbutt, Kenneth C. Cell, Vol. 124, Issue 1 https://doi.org/10.1016/j.cell.2005.10.033	journal	January 2006
Structural Basis of UV DNA-Damage Recognition by the DDB1–DDB2 Complex Scrima, Andrea; Koníčková, Renata; Czyzewski, Bryan K. Cell, Vol. 135, Issue 7 https://doi.org/10.1016/j.cell.2008.10.045	journal	December 2008
The Molecular Basis of CRL4DDB2/CSA Ubiquitin Ligase Architecture, Targeting, and Activation Fischer, Eric S.; Scrima, Andrea; Böhm, Kerstin Cell, Vol. 147, Issue 5 https://doi.org/10.1016/j.cell.2011.10.035	journal	November 2011
Premature Activation of the SLX4 Complex by Vpr Promotes G2/M Arrest and Escape from Innate Immune Sensing Laguette, Nadine; Brégnard, Christelle; Hue, Pauline Cell, Vol. 156, Issue 1-2 https://doi.org/10.1016/j.cell.2013.12.011	journal	January 2014
HIV-1 Accessory Proteins—Ensuring Viral Survival in a Hostile Environment Malim, Michael H.; Emerman, Michael Cell Host & Microbe, Vol. 3, Issue 6 https://doi.org/10.1016/j.chom.2008.04.008	journal	June 2008
Immune Evasion and Counteraction of Restriction Factors by HIV-1 and Other Primate Lentiviruses Kirchhoff, Frank Cell Host & Microbe, Vol. 8, Issue 1 https://doi.org/10.1016/j.chom.2010.06.004	journal	July 2010
Vpr Overcomes Macrophage-Specific Restriction of HIV-1 Env Expression and Virion Production Mashiba, Michael; Collins, David R.; Terry, Valeri H. Cell Host & Microbe, Vol. 16, Issue 6 https://doi.org/10.1016/j.chom.2014.10.014	journal	December 2014
Vpr Overcomes Macrophage-Specific Restriction of HIV-1 Env Expression and Virion Production Mashiba, Michael; Collins, David R.; Terry, Valeri H. Cell Host & Microbe, Vol. 17, Issue 3 https://doi.org/10.1016/j.chom.2015.02.016	journal	March 2015
Molecular Determinants for Recognition of Divergent SAMHD1 Proteins by the Lentiviral Accessory Protein Vpx Schwefel, David; Boucherit, Virginie C.; Christodoulou, Evangelos Cell Host & Microbe, Vol. 17, Issue 4 https://doi.org/10.1016/j.chom.2015.03.004	journal	April 2015
HIV accessory proteins versus host restriction factors Strebel, Klaus Current Opinion in Virology, Vol. 3, Issue 6 https://doi.org/10.1016/j.coviro.2013.08.004	journal	December 2013
DCAFs, the Missing Link of the CUL4-DDB1 Ubiquitin Ligase Lee, Jennifer; Zhou, Pengbo Molecular Cell, Vol. 26, Issue 6 https://doi.org/10.1016/j.molcel.2007.06.001	journal	June 2007
Molecular architecture and assembly of the DDB1–CUL4A ubiquitin ligase machinery Angers, Stephane; Li, Ti; Yi, Xianhua Nature, Vol. 443, Issue 7111 https://doi.org/10.1038/nature05175	journal	October 2006
Enzymatic capture of an extrahelical thymine in the search for uracil in DNA Parker, Jared B.; Bianchet, Mario A.; Krosky, Daniel J. Nature, Vol. 449, Issue 7161 https://doi.org/10.1038/nature06131	journal	August 2007
Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein Hrecka, Kasia; Hao, Caili; Gierszewska, Magda Nature, Vol. 474, Issue 7353 https://doi.org/10.1038/nature10195	journal	June 2011
HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase Goldstone, David C.; Ennis-Adeniran, Valerie; Hedden, Joseph J. Nature, Vol. 480, Issue 7377 https://doi.org/10.1038/nature10623	journal	November 2011
Structural basis of lentiviral subversion of a cellular protein degradation pathway Schwefel, David; Groom, Harriet C. T.; Boucherit, Virginie C. Nature, Vol. 505, Issue 7482 https://doi.org/10.1038/nature12815	journal	December 2013
Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide Fischer, Eric S.; Böhm, Kerstin; Lydeard, John R. Nature, Vol. 512, Issue 7512 https://doi.org/10.1038/nature13527	journal	July 2014
A promiscuous α-helical motif anchors viral hijackers and substrate receptors to the CUL4–DDB1 ubiquitin ligase machinery Li, Ti; Robert, Eva I.; van Breugel, Pieter C. Nature Structural & Molecular Biology, Vol. 17, Issue 1 https://doi.org/10.1038/nsmb.1719	journal	December 2009
HIV-1 Vpr function is mediated by interaction with the damage-specific DNA-binding protein DDB1 Schrofelbauer, B.; Hakata, Y.; Landau, N. R. Proceedings of the National Academy of Sciences, Vol. 104, Issue 10 https://doi.org/10.1073/pnas.0610167104	journal	February 2007
Lentiviral Vpr usurps Cul4-DDB1[VprBP] E3 ubiquitin ligase to modulate cell cycle Hrecka, K.; Gierszewska, M.; Srivastava, S. Proceedings of the National Academy of Sciences, Vol. 104, Issue 28 https://doi.org/10.1073/pnas.0702102104	journal	July 2007
HIV DNA is heavily uracilated, which protects it from autointegration Yan, N.; O'Day, E.; Wheeler, L. A. Proceedings of the National Academy of Sciences, Vol. 108, Issue 22 https://doi.org/10.1073/pnas.1102943108	journal	May 2011
Damaged DNA induced UV-damaged DNA-binding protein (UV-DDB) dimerization and its roles in chromatinized DNA repair Yeh, J. I.; Levine, A. S.; Du, S. Proceedings of the National Academy of Sciences, Vol. 109, Issue 41 https://doi.org/10.1073/pnas.1110067109	journal	July 2012
Uracil DNA glycosylase initiates degradation of HIV-1 cDNA containing misincorporated dUTP and prevents viral integration Weil, A. F.; Ghosh, D.; Zhou, Y. Proceedings of the National Academy of Sciences, Vol. 110, Issue 6 https://doi.org/10.1073/pnas.1219702110	journal	January 2013
HIV-1 and HIV-2 exhibit divergent interactions with HLTF and UNG2 DNA repair proteins Hrecka, Kasia; Hao, Caili; Shun, Ming-Chieh Proceedings of the National Academy of Sciences, Vol. 113, Issue 27 https://doi.org/10.1073/pnas.1605023113	journal	June 2016
HIV-1 Vpr Loads Uracil DNA Glycosylase-2 onto DCAF1, a Substrate Recognition Subunit of a Cullin 4A-RING E3 Ubiquitin Ligase for Proteasome-dependent Degradation Ahn, Jinwoo; Vu, Thomas; Novince, Zach Journal of Biological Chemistry, Vol. 285, Issue 48 https://doi.org/10.1074/jbc.M110.133181	journal	September 2010
HIV/Simian Immunodeficiency Virus (SIV) Accessory Virulence Factor Vpx Loads the Host Cell Restriction Factor SAMHD1 onto the E3 Ubiquitin Ligase Complex CRL4 ^DCAF1 Ahn, Jinwoo; Hao, Caili; Yan, Junpeng Journal of Biological Chemistry, Vol. 287, Issue 15 https://doi.org/10.1074/jbc.M112.340711	journal	February 2012
Frequent Incorporation of Ribonucleotides during HIV-1 Reverse Transcription and Their Attenuated Repair in Macrophages Kennedy, Edward M.; Amie, Sarah M.; Bambara, Robert A. Journal of Biological Chemistry, Vol. 287, Issue 17 https://doi.org/10.1074/jbc.M112.348482	journal	March 2012
HIV-2 and SIVmac Accessory Virulence Factor Vpx Down-regulates SAMHD1 Enzyme Catalysis Prior to Proteasome-dependent Degradation DeLucia, Maria; Mehrens, Jennifer; Wu, Ying Journal of Biological Chemistry, Vol. 288, Issue 26 https://doi.org/10.1074/jbc.M113.469007	journal	May 2013
HIV-1 Vpr Protein Enhances Proteasomal Degradation of MCM10 DNA Replication Factor through the Cul4-DDB1[VprBP] E3 Ubiquitin Ligase to Induce G ₂ /M Cell Cycle Arrest Romani, Bizhan; Shaykh Baygloo, Nima; Aghasadeghi, Mohammad Reza Journal of Biological Chemistry, Vol. 290, Issue 28 https://doi.org/10.1074/jbc.M115.641522	journal	June 2015
Structural Basis of Clade-specific Engagement of SAMHD1 (Sterile α Motif and Histidine/Aspartate-containing Protein 1) Restriction Factors by Lentiviral Viral Protein X (Vpx) Virulence Factors Wu, Ying; Koharudin, Leonardus M. I.; Mehrens, Jennifer Journal of Biological Chemistry, Vol. 290, Issue 29 https://doi.org/10.1074/jbc.M115.665513	journal	June 2015
Vpr-mediated Incorporation of UNG2 into HIV-1 Particles Is Required to Modulate the Virus Mutation Rate and for Replication in Macrophages Chen, Renxiang; Le Rouzic, Erwann; Kearney, Jessica A. Journal of Biological Chemistry, Vol. 279, Issue 27 https://doi.org/10.1074/jbc.M403875200	journal	April 2004
The HIV1 Protein Vpr Acts to Promote G ₂ Cell Cycle Arrest by Engaging a DDB1 and Cullin4A-containing Ubiquitin Ligase Complex Using VprBP/DCAF1 as an Adaptor Wen, Xiaoyun; Duus, Karen M.; Friedrich, Thomas D. Journal of Biological Chemistry, Vol. 282, Issue 37 https://doi.org/10.1074/jbc.M703955200	journal	July 2007
Vpr expression abolishes the capacity of HIV-1 infected cells to repair uracilated DNA Eldin, Patrick; Chazal, Nathalie; Fenard, David Nucleic Acids Research, Vol. 42, Issue 3 https://doi.org/10.1093/nar/gkt974	journal	October 2013
The role of HIV-1 Vpr in promoting the infection of nondividing cells and in cell cycle arrest Sharifi, Hamayun J.; Furuya, Andrea M.; de Noronha, Carlos M. C. Current Opinion in HIV and AIDS, Vol. 7, Issue 2 https://doi.org/10.1097/COH.0b013e32835049e0	journal	January 2012
APOBEC proteins and intrinsic resistance to HIV-1 infection Malim, Michael H. Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 364, Issue 1517 https://doi.org/10.1098/rstb.2008.0185	journal	November 2008
Base Excision Repair Krokan, H. E.; Bjoras, M. Cold Spring Harbor Perspectives in Biology, Vol. 5, Issue 4 https://doi.org/10.1101/cshperspect.a012583	journal	April 2013
Refinement of severely incomplete structures with maximum likelihood in BUSTER–TNT Blanc, E.; Roversi, P.; Vonrhein, C. Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12 https://doi.org/10.1107/S0907444904016427	journal	November 2004
Considerations for the refinement of low-resolution crystal structures DeLaBarre, Byron; Brunger, Axel T. Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 8 https://doi.org/10.1107/S0907444906012650	journal	July 2006
Linking Crystallographic Model and Data Quality Karplus, P. A.; Diederichs, K. Science, Vol. 336, Issue 6084 https://doi.org/10.1126/science.1218231	journal	May 2012
DDB1 and Cul4A Are Required for Human Immunodeficiency Virus Type 1 Vpr-Induced G2 Arrest Tan, Lindi; Ehrlich, Elana; Yu, Xiao-Fang Journal of Virology, Vol. 81, Issue 19 https://doi.org/10.1128/JVI.01380-07	journal	July 2007
Recruitment of the Nuclear Form of Uracil DNA Glycosylase into Virus Particles Participates in the Full Infectivity of HIV-1 Guenzel, C. A.; Herate, C.; Le Rouzic, E. Journal of Virology, Vol. 86, Issue 5 https://doi.org/10.1128/JVI.05163-11	journal	December 2011
Isolation of Human Immunodeficiency Virus Type 1 Cores: Retention of Vpr in the Absence of p6gag Accola, Molly A.; Öhagen, Åsa; Göttlinger, Heinrich G. Journal of Virology, Vol. 74, Issue 13 https://doi.org/10.1128/JVI.74.13.6198-6202.2000	journal	July 2000
Uracil DNA Glycosylase Is Dispensable for Human Immunodeficiency Virus Type 1 Replication and Does Not Contribute to the Antiviral Effects of the Cytidine Deaminase Apobec3G Kaiser, Shari M.; Emerman, Michael Journal of Virology, Vol. 80, Issue 2 https://doi.org/10.1128/JVI.80.2.875-882.2006	journal	January 2006
Molecular biology of the human immunodeficiency virus accessory proteins Subbramanian, R. A.; Cohen, E. A. Journal of Virology, Vol. 68, Issue 11 https://doi.org/10.1128/jvi.68.11.6831-6835.1994	journal	November 1994
Human immunodeficiency virus type 1 Vpr arrests the cell cycle in G2 by inhibiting the activation of p34cdc2-cyclin B Re, F.; Braaten, D.; Franke, E. K. Journal of Virology, Vol. 69, Issue 11 https://doi.org/10.1128/jvi.69.11.6859-6864.1995	journal	November 1995
The human immunodeficiency virus type 1 vpr gene prevents cell proliferation during chronic infection Rogel, M. E.; Wu, L. I.; Emerman, M. Journal of Virology, Vol. 69, Issue 2 https://doi.org/10.1128/jvi.69.2.882-888.1995	journal	February 1995
Human immunodeficiency virus type 1 Vpr protein binds to the uracil DNA glycosylase DNA repair enzyme Bouhamdan, M.; Benichou, S.; Rey, F. Journal of Virology, Vol. 70, Issue 2 https://doi.org/10.1128/jvi.70.2.697-704.1996	journal	February 1996
Uracil DNA glycosylase specifically interacts with Vpr of both human immunodeficiency virus type 1 and simian immunodeficiency virus of sooty mangabeys, but binding does not correlate with cell cycle arrest Selig, L.; Benichou, S.; Rogel, M. E. Journal of Virology, Vol. 71, Issue 6 https://doi.org/10.1128/jvi.71.6.4842-4846.1997	journal	June 1997
HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system DeHart, Jason L.; Zimmerman, Erik S.; Ardon, Orly Virology Journal, Vol. 4, Issue 1 https://doi.org/10.1186/1743-422X-4-57	journal	January 2007
Defining the Interactions and Role of DCAF1/VPRBP in the DDB1-Cullin4A E3 Ubiquitin Ligase Complex Engaged by HIV-1 Vpr to Induce a G2 Cell Cycle Arrest Gérard, Francine C. A.; Yang, Ruifeng; Romani, Bizhan PLoS ONE, Vol. 9, Issue 2 https://doi.org/10.1371/journal.pone.0089195	journal	February 2014
HIV-1 Vpr-Mediated G2 Arrest Involves the DDB1-CUL4AVPRBP E3 Ubiquitin Ligase Belzile, Jean-Philippe; Duisit, Ghislaine; Rougeau, Nicole PLoS Pathogens, Vol. 3, Issue 7 https://doi.org/10.1371/journal.ppat.0030085	journal	January 2007
Primate Lentiviral Vpx Commandeers DDB1 to Counteract a Macrophage Restriction Sharova, Natalia; Wu, Yuanfei; Zhu, Xiaonan PLoS Pathogens, Vol. 4, Issue 5 https://doi.org/10.1371/journal.ppat.1000057	journal	May 2008
Lentiviral Vpx Accessory Factor Targets VprBP/DCAF1 Substrate Adaptor for Cullin 4 E3 Ubiquitin Ligase to Enable Macrophage Infection Srivastava, Smita; Swanson, Selene K.; Manel, Nicolas PLoS Pathogens, Vol. 4, Issue 5 https://doi.org/10.1371/journal.ppat.1000059	journal	May 2008
β -TrCP Dependency of HIV-1 Vpu-Induced Downregulation of CD4 and BST-2/Tetherin P. Blanchet, Fabien; P. Mitchell, J.; Piguet, Vincent Current HIV Research, Vol. 10, Issue 4 https://doi.org/10.2174/157016212800792441	journal	May 2012
Base Excision Repair Joshi-Tope, G. Reactome - a curated knowledgebase of biological pathways, Vol. 08 https://doi.org/10.3180/react_1104.1	journal	March 2004
Base Excision Repair Orlic-Milacic, M. Reactome - a curated knowledgebase of biological pathways, Vol. 52 https://doi.org/10.3180/react_1104.3	journal	March 2015
Suppression of APOBEC3-mediated restriction of HIV-1 by Vif Feng, Yuqing; Baig, Tayyba T.; Love, Robin P. Frontiers in Microbiology, Vol. 5 https://doi.org/10.3389/fmicb.2014.00450	journal	August 2014
HIV1 Vpr Arrests the Cell Cycle by Recruiting DCAF1/VprBP, a Receptor of the Cul4-DDB1 Ubiquitin Ligase Le Rouzic, Erwann; Belaïdouni, Nadia; Estrabaud, Emilie Cell Cycle, Vol. 6, Issue 2 https://doi.org/10.4161/cc.6.2.3732	journal	January 2007

Cited By (15)

CRL4Mahj E3 ubiquitin ligase promotes neural stem cell reactivation Ly, Phuong Thao; Tan, Ye Sing; Koe, Chwee Tat PLOS Biology, Vol. 17, Issue 6 https://doi.org/10.1371/journal.pbio.3000276	journal	June 2019
Proteasomal Degradation Machinery: Favorite Target of HIV-1 Proteins Lata, Sneh; Mishra, Ritu; Banerjea, Akhil C. Frontiers in Microbiology, Vol. 9 https://doi.org/10.3389/fmicb.2018.02738	journal	November 2018
Vpr and Its Cellular Interaction Partners: R We There Yet? Fabryova, Helena; Strebel, Klaus Cells, Vol. 8, Issue 11 https://doi.org/10.3390/cells8111310	journal	October 2019
The HIV-1 Vpr Protein: A Multifaceted Target for Therapeutic Intervention González, María International Journal of Molecular Sciences, Vol. 18, Issue 1 https://doi.org/10.3390/ijms18010126	journal	January 2017
HIV-1 Integrase-Targeted Short Peptides Derived from a Viral Protein R Sequence Zhao, Xue; Métifiot, Mathieu; Kiselev, Evgeny Molecules, Vol. 23, Issue 8 https://doi.org/10.3390/molecules23081858	journal	July 2018
A Role for the Host DNA Damage Response in Hepatitis B Virus cccDNA Formation—and Beyond? Schreiner, Sabrina; Nassal, Michael Viruses, Vol. 9, Issue 5 https://doi.org/10.3390/v9050125	journal	May 2017
Hijacking of the Ubiquitin/Proteasome Pathway by the HIV Auxiliary Proteins Seissler, Tanja; Marquet, Roland; Paillart, Jean-Christophe Viruses, Vol. 9, Issue 11 https://doi.org/10.3390/v9110322	journal	October 2017
Mannose receptor is an HIV restriction factor counteracted by Vpr in macrophages Lubow, Jay; Virgilio, Maria C.; Merlino, Madeline eLife, Vol. 9 https://doi.org/10.7554/elife.51035	journal	March 2020
New paradigm of functional regulation by DNA mimic proteins: Recent updates Wang, Hao‐Ching; Chou, Chia‐Cheng; Hsu, Kai‐Cheng IUBMB Life, Vol. 71, Issue 5 https://doi.org/10.1002/iub.1992	journal	December 2018
WD40 repeat domain proteins: a novel target class? Schapira, Matthieu; Tyers, Mike; Torrent, Maricel Nature Reviews Drug Discovery, Vol. 16, Issue 11 https://doi.org/10.1038/nrd.2017.179	journal	October 2017
Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex Bussiere, Dirksen E.; Xie, Lili; Srinivas, Honnappa Nature Chemical Biology, Vol. 16, Issue 1 https://doi.org/10.1038/s41589-019-0411-6	journal	December 2019
Mannose receptor is a restriction factor of HIV in macrophages and is counteracted by the accessory protein Vpr Lubow, Jay; Collins, David R.; Mashiba, Mike https://doi.org/10.1101/742197	posted_content	August 2019
Is Uracil-DNA Glycosylase UNG2 a New Cellular Weapon Against HIV-1? Kara, Hesna; Chazal, Nathalie; Bouaziz, Serge Current HIV Research, Vol. 17, Issue 3 https://doi.org/10.2174/1570162x17666190821154331	journal	October 2019
Illuminating the Role of Vpr in HIV Infection of Myeloid Cells Nodder, Sarah Beth; Gummuluru, Suryaram Frontiers in Immunology, Vol. 10 https://doi.org/10.3389/fimmu.2019.01606	journal	July 2019
Distinct MCM10 Proteasomal Degradation Profiles by Primate Lentiviruses Vpr Proteins Chang, Hao; Siarot, Lowela; Matsuura, Ryosuke Viruses, Vol. 12, Issue 1 https://doi.org/10.3390/v12010098	journal	January 2020

Similar Records

Structural Basis of Clade-specific Engagement of SAMHD1 (Sterile α Motif and Histidine/Aspartate-containing Protein 1) Restriction Factors by Lentiviral Viral Protein X (Vpx) Virulence Factors

Journal Article · Thu Jun 04 00:00:00 EDT 2015 · Journal of Biological Chemistry · OSTI ID:1245873

The poly-proline tail of SIVmac Vpx provides gain of function for resistance to a cryptic proteasome-dependent degradation pathway

Journal Article · Tue Nov 14 23:00:00 EST 2017 · Virology · OSTI ID:22722971

HD domain of SAMHD1 influences Vpx-induced degradation at a post-interaction step

Journal Article · Thu Feb 11 23:00:00 EST 2016 · Biochemical and Biophysical Research Communications · OSTI ID:22594241

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
X-ray crystallography
virology

The DDB1–DCAF1–Vpr–UNG2 crystal structure reveals how HIV-1 Vpr steers human UNG2 toward destruction

Citation Formats

References (63)

Cited By (15)

Similar Records

Related Subjects