Structural determinants of nuclear export signal orientation in binding to exportin CRM1

Fung, Ho Yee Joyce; Fu, Szu -Chin; Brautigam, Chad A.; Chook, Yuh Min

doi:10.7554/eLife.10034

Structural determinants of nuclear export signal orientation in binding to exportin CRM1

Journal Article · Tue Sep 08 00:00:00 EDT 2015 · eLife

DOI:https://doi.org/10.7554/eLife.10034· OSTI ID:1223794

^[1]; Fu, Szu -Chin ^[1]; Brautigam, Chad A. ^[1]; Chook, Yuh Min ^[1]

Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)

The Chromosome Region of Maintenance 1 (CRM1) protein mediates nuclear export of hundreds of proteins through recognition of their nuclear export signals (NESs), which are highly variable in sequence and structure. The plasticity of the CRM1-NES interaction is not well understood, as there are many NES sequences that seem incompatible with structures of the NES-bound CRM1 groove. Crystal structures of CRM1 bound to two different NESs with unusual sequences showed the NES peptides binding the CRM1 groove in the opposite orientation (minus) to that of previously studied NESs (plus). A comparison of minus and plus NESs identified structural and sequence determinants for NES orientation. The binding of NESs to CRM1 in both orientations results in a large expansion in NES consensus patterns and therefore a corresponding expansion of potential NESs in the proteome.

View Accepted Manuscript (DOE)

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

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1223794

Alternate ID(s):: OSTI ID: 1856372

Journal Information:: eLife, Journal Name: eLife Vol. 4; ISSN 2050-084X

Publisher:: eLife Sciences Publications, Ltd.Copyright Statement

Country of Publication:: United States

Language:: English

References (52)

Structural basis of recognition of monopartite and bipartite nuclear localization sequences by mammalian importin-α11Edited by K. Nagai Fontes, Marcos R. M.; Teh, Trazel; Kobe, Bostjan Journal of Molecular Biology, Vol. 297, Issue 5 https://doi.org/10.1006/jmbi.2000.3642	journal	April 2000
Exploring the gas access routes in a [NiFeSe] hydrogenase using crystals pressurized with krypton and oxygen Zacarias, Sónia; Temporão, Adriana; Carpentier, Philippe JBIC Journal of Biological Inorganic Chemistry, Vol. 25, Issue 6 https://doi.org/10.1007/s00775-020-01814-y	journal	August 2020
Crystal structure of human Karyopherin β2 bound to the PY-NLS of Saccharomyces cerevisiae Nab2 Soniat, Michael; Sampathkumar, Parthasarathy; Collett, Garen Journal of Structural and Functional Genomics, Vol. 14, Issue 2 https://doi.org/10.1007/s10969-013-9150-1	journal	March 2013
CRM1 Is an Export Receptor for Leucine-Rich Nuclear Export Signals Fornerod, Maarten; Ohno, Mutsuhito; Yoshida, Minoru Cell, Vol. 90, Issue 6 https://doi.org/10.1016/S0092-8674(00)80371-2	journal	September 1997
Crystallographic Analysis of the Recognition of a Nuclear Localization Signal by the Nuclear Import Factor Karyopherin α Conti, Elena; Uy, Marc; Leighton, Lore Cell, Vol. 94, Issue 2 https://doi.org/10.1016/S0092-8674(00)81419-1	journal	July 1998
Calculations and Publication-Quality Illustrations for Analytical Ultracentrifugation Data Brautigam, Chad A. Methods in Enzymology https://doi.org/10.1016/bs.mie.2015.05.001	book	January 2015
Crystal structure of the karyopherin Kap121p bound to the extreme C-terminus of the protein phosphatase Cdc14p Kobayashi, Junya; Hirano, Hidemi; Matsuura, Yoshiyuki Biochemical and Biophysical Research Communications, Vol. 463, Issue 3 https://doi.org/10.1016/j.bbrc.2015.05.060	journal	July 2015
Rules for Nuclear Localization Sequence Recognition by Karyopherinβ2 Lee, Brittany J.; Cansizoglu, Ahmet E.; Süel, Katherine E. Cell, Vol. 126, Issue 3 https://doi.org/10.1016/j.cell.2006.05.049	journal	August 2006
Structural Insights into How Yrb2p Accelerates the Assembly of the Xpo1p Nuclear Export Complex Koyama, Masako; Shirai, Natsuki; Matsuura, Yoshiyuki Cell Reports, Vol. 9, Issue 3 https://doi.org/10.1016/j.celrep.2014.09.052	journal	November 2014
Recognition of nuclear targeting signals by Karyopherin-β proteins Xu, Darui; Farmer, Alicia; Chook, Yuh Min Current Opinion in Structural Biology, Vol. 20, Issue 6 https://doi.org/10.1016/j.sbi.2010.09.008	journal	December 2010
Atomic basis of CRM1-cargo recognition, release and inhibition Fung, Ho Yee Joyce; Chook, Yuh Min Seminars in Cancer Biology, Vol. 27 https://doi.org/10.1016/j.semcancer.2014.03.002	journal	August 2014
Structural Analysis of the Interactions Between Paxillin LD Motifs and α-Parvin Lorenz, Sonja; Vakonakis, Ioannis; Lowe, Edward D. Structure, Vol. 16, Issue 10 https://doi.org/10.1016/j.str.2008.08.007	journal	October 2008
Leucine-rich nuclear-export signals: born to be weak Kutay, Ulrike; Güttinger, Stephan Trends in Cell Biology, Vol. 15, Issue 3 https://doi.org/10.1016/j.tcb.2005.01.005	journal	March 2005
Structure of importin-β bound to the IBB domain of importin-α Cingolani, Gino; Petosa, Carlo; Weis, Karsten Nature, Vol. 399, Issue 6733 https://doi.org/10.1038/20367	journal	May 1999
Structure of the nuclear transport complex karyopherin-β2–Ran˙GppNHp Chook, Yuh Min; Blobel, Günter Nature, Vol. 399, Issue 6733 https://doi.org/10.1038/20375	journal	May 1999
CRM1 is responsible for intracellular transport mediated by the nuclear export signal Fukuda, Makoto; Asano, Shiro; Nakamura, Takahiro Nature, Vol. 390, Issue 6657 https://doi.org/10.1038/36894	journal	November 1997
Structural determinants of peptide-binding orientation and of sequence specificity in SH3 domains Lim, Wendell A.; Richards, Frederic M.; Fox, Robert O. Nature, Vol. 372, Issue 6504 https://doi.org/10.1038/372375a0	journal	November 1994
Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates Ng, Cherlyn; Jackson, Rebecca A.; Buschdorf, Jan P. The EMBO Journal, Vol. 27, Issue 5 https://doi.org/10.1038/emboj.2008.18	journal	February 2008
Structural basis for competitive interactions of Pex14 with the import receptors Pex5 and Pex19 Neufeld, Christian; Filipp, Fabian V.; Simon, Bernd The EMBO Journal, Vol. 28, Issue 6 https://doi.org/10.1038/emboj.2009.7	journal	February 2009
An allosteric mechanism to displace nuclear export cargo from CRM1 and RanGTP by RanBP1 Koyama, Masako; Matsuura, Yoshiyuki The EMBO Journal, Vol. 29, Issue 12 https://doi.org/10.1038/emboj.2010.89	journal	May 2010
Antileukemic activity of nuclear export inhibitors that spare normal hematopoietic cells Etchin, J.; Sun, Q.; Kentsis, A. Leukemia, Vol. 27, Issue 1 https://doi.org/10.1038/leu.2012.219	journal	July 2012
Structural basis for leucine-rich nuclear export signal recognition by CRM1 Dong, Xiuhua; Biswas, Anindita; Süel, Katherine E. Nature, Vol. 458, Issue 7242 https://doi.org/10.1038/nature07975	journal	April 2009
Recognition of a signal peptide by the signal recognition particle Janda, Claudia Y.; Li, Jade; Oubridge, Chris Nature, Vol. 465, Issue 7297 https://doi.org/10.1038/nature08870	journal	April 2010
Nuclear export inhibitors avert progression in preclinical models of inflammatory demyelination Haines, Jeffery D.; Herbin, Olivier; de la Hera, Belén Nature Neuroscience, Vol. 18, Issue 4 https://doi.org/10.1038/nn.3953	journal	February 2015
NES consensus redefined by structures of PKI-type and Rev-type nuclear export signals bound to CRM1 Güttler, Thomas; Madl, Tobias; Neumann, Piotr Nature Structural & Molecular Biology, Vol. 17, Issue 11 https://doi.org/10.1038/nsmb.1931	journal	October 2010
HBP1 and Mad1 repressors bind the Sin3 corepressor PAH2 domain with opposite helical orientations Swanson, Kurt A.; Knoepfler, Paul S.; Huang, Kai Nature Structural & Molecular Biology, Vol. 11, Issue 8 https://doi.org/10.1038/nsmb798	journal	July 2004
PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome Sharma, Deepti; De Falco, Louis; Padavattan, Sivaraman Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-13641-0	journal	December 2019
Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation Tillu, Vikas A.; Rae, James; Gao, Ya Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-21035-4	journal	February 2021
The oligomeric structures of plant cryptochromes Shao, Kai; Zhang, Xue; Li, Xu Nature Structural & Molecular Biology, Vol. 27, Issue 5 https://doi.org/10.1038/s41594-020-0420-x	journal	May 2020
Nuclear localization signals for four distinct karyopherin-β nuclear import systems Soniat, Michael; Chook, Yuh Min Biochemical Journal, Vol. 468, Issue 3 https://doi.org/10.1042/BJ20150368	journal	June 2015
Nuclear export inhibition through covalent conjugation and hydrolysis of Leptomycin B by CRM1 Sun, Qingxiang; Carrasco, Yazmin P.; Hu, Youcai Proceedings of the National Academy of Sciences, Vol. 110, Issue 4 https://doi.org/10.1073/pnas.1217203110	journal	January 2013
Small Ubiquitin-like Modifier (SUMO) Recognition of a SUMO Binding Motif: A REVERSAL OF THE BOUND ORIENTATION Song, Jing; Zhang, Ziming; Hu, Weidong Journal of Biological Chemistry, Vol. 280, Issue 48 https://doi.org/10.1074/jbc.M507059200	journal	October 2005
NESdb: a database of NES-containing CRM1 cargoes Xu, Darui; Grishin, Nick V.; Chook, Yuh Min Molecular Biology of the Cell, Vol. 23, Issue 18 https://doi.org/10.1091/mbc.E12-01-0045	journal	September 2012
Sequence and structural analyses of nuclear export signals in the NESdb database Xu, Darui; Farmer, Alicia; Collett, Garen Molecular Biology of the Cell, Vol. 23, Issue 18 https://doi.org/10.1091/mbc.E12-01-0046	journal	September 2012
LocNES: a computational tool for locating classical NESs in CRM1 cargo proteins Xu, Darui; Marquis, Kara; Pei, Jimin Bioinformatics, Vol. 31, Issue 9 https://doi.org/10.1093/bioinformatics/btu826	journal	December 2014
Prediction of leucine-rich nuclear export signal containing proteins with NESsential Fu, Szu-Chin; Imai, Kenichiro; Horton, Paul Nucleic Acids Research, Vol. 39, Issue 16 https://doi.org/10.1093/nar/gkr493	journal	June 2011
ValidNESs: a database of validated leucine-rich nuclear export signals Fu, Szu-Chin; Huang, Hsuan-Cheng; Horton, Paul Nucleic Acids Research, Vol. 41, Issue D1 https://doi.org/10.1093/nar/gks936	journal	October 2012
Analysis and prediction of leucine-rich nuclear export signals la Cour, Tanja; Kiemer, Lars; Mølgaard, Anne Protein Engineering, Design and Selection, Vol. 17, Issue 6 https://doi.org/10.1093/protein/gzh062	journal	June 2004
HKL -3000: the integration of data reduction and structure solution – from diffraction images to an initial model in minutes Minor, Wladek; Cymborowski, Marcin; Otwinowski, Zbyszek Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 8 https://doi.org/10.1107/S0907444906019949	journal	July 2006
Averaged kick maps: less noise, more signal…and probably less bias Pražnikar, Jure; Afonine, Pavel V.; Gunčar, Gregor Acta Crystallographica Section D Biological Crystallography, Vol. 65, Issue 9 https://doi.org/10.1107/S0907444909021933	journal	August 2009
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
Towards automated crystallographic structure refinement with phenix.refine Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Echols, Nathaniel Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4 https://doi.org/10.1107/S0907444912001308	journal	March 2012
Nuclear Export Signal Consensus Sequences Defined Using a Localization-Based Yeast Selection System Kosugi, Shunichi; Hasebe, Masako; Tomita, Masaru Traffic, Vol. 9, Issue 12 https://doi.org/10.1111/j.1600-0854.2008.00825.x	journal	December 2008
Crystal Structure of the Nuclear Export Receptor CRM1 in Complex with Snurportin1 and RanGTP Monecke, T.; Guttler, T.; Neumann, P. Science, Vol. 324, Issue 5930 https://doi.org/10.1126/science.1173388	journal	April 2009
Evidence for a Role of CRM1 in Signal-Mediated Nuclear Protein Export Ossareh-Nazari, Batool; Bachelerie, Françoise; Dargemont, Catherine Science, Vol. 278, Issue 5335 https://doi.org/10.1126/science.278.5335.141	journal	October 1997
Two binding orientations for peptides to the Src SH3 domain: development of a general model for SH3-ligand interactions Feng, S.; Chen, J.; Yu, H. Science, Vol. 266, Issue 5188 https://doi.org/10.1126/science.7526465	journal	November 1994
Signal Recognition Particle: An Essential Protein-Targeting Machine Akopian, David; Shen, Kuang; Zhang, Xin Annual Review of Biochemistry, Vol. 82, Issue 1 https://doi.org/10.1146/annurev-biochem-072711-164732	journal	June 2013
Selective inhibitors of nuclear export show that CRM1/XPO1 is a target in chronic lymphocytic leukemia Lapalombella, Rosa; Sun, Qingxiang; Williams, Katie Blood, Vol. 120, Issue 23 https://doi.org/10.1182/blood-2012-05-429506	journal	November 2012
PHENIX: a comprehensive Python-based system for macromolecular structure solution. Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.45787	text	January 2010
Structural basis for competitive interactions of Pex14 with the import receptors Pex5 and Pex19 Neufeld, C.; Filipp, F. V.; Simon, B. Deutsches Elektronen-Synchrotron, DESY, Hamburg https://doi.org/10.3204/phppubdb-12665	text	January 2009

Cited By (20)

Nicotiana benthamiana exportin 1 is required for elicitor-induced phytoalexin production, cell death induction, and resistance against potato late blight pathogen Phytophthora infestans Mizuno, Yuri; Imano, Sayaka; Camagna, Maurizio Journal of General Plant Pathology, Vol. 85, Issue 5 https://doi.org/10.1007/s10327-019-00855-9	journal	April 2019
Next-generation XPO1 inhibitor shows improved efficacy and in vivo tolerability in hematological malignancies Hing, Z. A.; Fung, H. Y. J.; Ranganathan, P. Leukemia, Vol. 30, Issue 12 https://doi.org/10.1038/leu.2016.136	journal	May 2016
Active nuclear import and passive nuclear export are the primary determinants of TDP-43 localization Pinarbasi, Emile S.; Cağatay, Tolga; Fung, Ho Yee Joyce Scientific Reports, Vol. 8, Issue 1 https://doi.org/10.1038/s41598-018-25008-4	journal	May 2018
Structural prerequisites for CRM1-dependent nuclear export signaling peptides: accessibility, adapting conformation, and the stability at the binding site Lee, Yoonji; Pei, Jimin; Baumhardt, Jordan M. Scientific Reports, Vol. 9, Issue 1 https://doi.org/10.1038/s41598-019-43004-0	journal	April 2019
Nuclear export of ubiquitinated proteins via the UBIN-POST system Hirayama, Shoshiro; Sugihara, Munechika; Morito, Daisuke Proceedings of the National Academy of Sciences, Vol. 115, Issue 18 https://doi.org/10.1073/pnas.1711017115	journal	April 2018
Xpo7 is a broad-spectrum exportin and a nuclear import receptor Aksu, Metin; Pleiner, Tino; Karaca, Samir Journal of Cell Biology, Vol. 217, Issue 7 https://doi.org/10.1083/jcb.201712013	journal	May 2018
Structural basis for the nuclear import and export functions of the biportin Pdr6/Kap122 Aksu, Metin; Trakhanov, Sergei; Vera Rodriguez, Arturo The Journal of Cell Biology, Vol. 218, Issue 6 https://doi.org/10.1083/jcb.201812093	journal	April 2019
Proteome-level assessment of origin, prevalence and function of leucine-aspartic acid (LD) motifs Alam, Tanvir; Alazmi, Meshari; Naser, Rayan Bioinformatics https://doi.org/10.1093/bioinformatics/btz703	journal	October 2019
Exportin Crm1 is repurposed as a docking protein to generate microtubule organizing centers at the nuclear pore Bao, Xun X.; Spanos, Christos; Kojidani, Tomoko https://doi.org/10.1101/216838	posted_content	November 2017
Proteome-level assessment of origin, prevalence and function of Leucine-Aspartic Acid (LD) motifs Alam, Tanvir; Alazmi, Meshari; Naser, Rayan Bioinformatics https://doi.org/10.1101/278903	posted_content	March 2018
Dimerization of human Rio2 kinase/ATPase locks its ATP-binding site in an apo state Maurice, Frédérique; Pérébaskine, Natacha; Fribourg, Sébastien RNA Biology https://doi.org/10.1101/553800	journal	August 2019
Role of a versatile peptide motif in controlling Hox nuclear export and autophagy in the Drosophila fat body Duffraisse, Marilyne; Paul, Rachel; Hudry, Bruno https://doi.org/10.1101/843383	posted_content	November 2019
NoLogo: a new statistical model highlights the diversity and suggests new classes of Crm1-dependent nuclear export signals Liku, Muluye E.; Legere, Elizabeth-Ann; Moses, Alan M. BMC Bioinformatics, Vol. 19, Issue 1 https://doi.org/10.1186/s12859-018-2076-7	journal	February 2018
Assembly of the small ribosomal subunit in yeast: mechanism and regulation Chaker-Margot, Malik RNA, Vol. 24, Issue 7 https://doi.org/10.1261/rna.066985.118	journal	April 2018
New Drosophila Circadian Clock Mutants Affecting Temperature Compensation Induced by Targeted Mutagenesis of Timeless Singh, Samarjeet; Giesecke, Astrid; Damulewicz, Milena Frontiers in Physiology, Vol. 10 https://doi.org/10.3389/fphys.2019.01442	journal	December 2019
Gli Proteins: Regulation in Development and Cancer Niewiadomski, Paweł; Niedziółka, Sylwia M.; Markiewicz, Łukasz Cells, Vol. 8, Issue 2 https://doi.org/10.3390/cells8020147	journal	February 2019
Viral Appropriation: Laying Claim to Host Nuclear Transport Machinery Tessier, Tanner M.; Dodge, Mackenzie J.; Prusinkiewicz, Martin A. Cells, Vol. 8, Issue 6 https://doi.org/10.3390/cells8060559	journal	June 2019
Nuclear export receptor CRM1 recognizes diverse conformations in nuclear export signals Fung, Ho Yee Joyce; Fu, Szu-Chin; Chook, Yuh Min eLife, Vol. 6 https://doi.org/10.7554/elife.23961	journal	March 2017
Exportin Crm1 is repurposed as a docking protein to generate microtubule organizing centers at the nuclear pore Bao, Xun X.; Spanos, Christos; Kojidani, Tomoko eLife, Vol. 7 https://doi.org/10.7554/elife.33465	journal	May 2018
Importin-9 wraps around the H2A-H2B core to act as nuclear importer and histone chaperone Padavannil, Abhilash; Sarkar, Prithwijit; Kim, Seung Joong eLife, Vol. 8 https://doi.org/10.7554/elife.43630	journal	March 2019

Similar Records

Nuclear export receptor CRM1 recognizes diverse conformations in nuclear export signals

Journal Article · Thu Mar 09 19:00:00 EST 2017 · eLife · OSTI ID:1510248

Correlation of CRM1-NES affinity with nuclear export activity

Journal Article · Tue Aug 14 20:00:00 EDT 2018 · Molecular Biology of the Cell · OSTI ID:1570748

Recognition of nuclear export signals by CRM1 carrying the oncogenic E571K mutation

Journal Article · Wed Jul 29 20:00:00 EDT 2020 · Molecular Biology of the Cell · OSTI ID:1659286

Related Subjects

59 BASIC BIOLOGICAL SCIENCES

Structural determinants of nuclear export signal orientation in binding to exportin CRM1

Citation Formats

References (52)

Cited By (20)

Similar Records

Related Subjects