CUL5-ARIH2 E3-E3 ubiquitin ligase structure reveals cullin-specific NEDD8 activation.
Journal
Nature chemical biology
ISSN: 1552-4469
Titre abrégé: Nat Chem Biol
Pays: United States
ID NLM: 101231976
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
02
01
2021
accepted:
06
07
2021
pubmed:
15
9
2021
medline:
13
10
2021
entrez:
14
9
2021
Statut:
ppublish
Résumé
An emerging mechanism of ubiquitylation involves partnering of two distinct E3 ligases. In the best-characterized E3-E3 pathways, ARIH-family RING-between-RING (RBR) E3s ligate ubiquitin to substrates of neddylated cullin-RING E3s. The E3 ARIH2 has been implicated in ubiquitylation of substrates of neddylated CUL5-RBX2-based E3s, including APOBEC3-family substrates of the host E3 hijacked by HIV-1 virion infectivity factor (Vif). However, the structural mechanisms remained elusive. Here structural and biochemical analyses reveal distinctive ARIH2 autoinhibition, and activation on assembly with neddylated CUL5-RBX2. Comparison to structures of E3-E3 assemblies comprising ARIH1 and neddylated CUL1-RBX1-based E3s shows cullin-specific regulation by NEDD8. Whereas CUL1-linked NEDD8 directly recruits ARIH1, CUL5-linked NEDD8 does not bind ARIH2. Instead, the data reveal an allosteric mechanism. NEDD8 uniquely contacts covalently linked CUL5, and elicits structural rearrangements that unveil cryptic ARIH2-binding sites. The data reveal how a ubiquitin-like protein induces protein-protein interactions indirectly, through allostery. Allosteric specificity of ubiquitin-like protein modifications may offer opportunities for therapeutic targeting.
Identifiants
pubmed: 34518685
doi: 10.1038/s41589-021-00858-8
pii: 10.1038/s41589-021-00858-8
pmc: PMC8460447
mid: EMS129591
doi:
Substances chimiques
Cullin Proteins
0
NEDD8 Protein
0
NEDD8 protein, human
0
ARIH2 protein, human
EC 2.3.2.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1075-1083Subventions
Organisme : European Research Council
ID : 789016
Pays : International
Informations de copyright
© 2021. The Author(s).
Références
Komander, D. & Rape, M. The ubiquitin code. Annu. Rev. Biochem. 81, 203–229 (2012).
doi: 10.1146/annurev-biochem-060310-170328
pubmed: 22524316
Husnjak, K. & Dikic, I. Ubiquitin-binding proteins: decoders of ubiquitin-mediated cellular functions. Annu. Rev. Biochem. 81, 291–322 (2012).
pubmed: 22482907
doi: 10.1146/annurev-biochem-051810-094654
Pan, Z. Q., Kentsis, A., Dias, D. C., Yamoah, K. & Wu, K. Nedd8 on cullin: building an expressway to protein destruction. Oncogene 23, 1985–1997 (2004).
pubmed: 15021886
doi: 10.1038/sj.onc.1207414
Rusnac, D. V. & Zheng, N. Structural biology of CRL ubiquitin ligases. Adv. Exp. Med Biol. 1217, 9–31 (2020).
pubmed: 31898219
doi: 10.1007/978-981-15-1025-0_2
Zheng, N. et al. Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex. Nature 416, 703–709 (2002).
pubmed: 11961546
doi: 10.1038/416703a
Kamura, T. et al. VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases. Genes Dev. 18, 3055–3065 (2004).
pubmed: 15601820
pmcid: 535916
doi: 10.1101/gad.1252404
Huang, D. T. et al. E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification. Mol. Cell 33, 483–495 (2009).
pubmed: 19250909
pmcid: 2725360
doi: 10.1016/j.molcel.2009.01.011
Stanley, D. J. et al. Inhibition of a NEDD8 cascade restores restriction of HIV by APOBEC3G. PLoS Pathog. 8, e1003085 (2012).
pubmed: 23300442
pmcid: 3531493
doi: 10.1371/journal.ppat.1003085
Huttenhain, R. et al. ARIH2 is a Vif-dependent regulator of CUL5-mediated APOBEC3G degradation in HIV infection. Cell Host Microbe 26, 86–99 e87 (2019).
pubmed: 31253590
pmcid: 7153695
doi: 10.1016/j.chom.2019.05.008
Kabir, S. et al. The CUL5 ubiquitin ligase complex mediates resistance to CDK9 and MCL1 inhibitors in lung cancer cells. eLife https://doi.org/10.7554/eLife.44288 (2019).
Hundley, F. V. et al. A comprehensive phenotypic CRISPR-Cas9 screen of the ubiquitin pathway uncovers roles of ubiquitin ligases in mitosis. Mol. Cell https://doi.org/10.1016/j.molcel.2021.01.014 (2021).
Duda, D. M. et al. Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation. Cell 134, 995–1006 (2008).
pubmed: 18805092
pmcid: 2628631
doi: 10.1016/j.cell.2008.07.022
Baek, K., Scott, D. C. & Schulman, B. A. NEDD8 and ubiquitin ligation by cullin-RING E3 ligases. Curr. Opin. Struct. Biol. 67, 101–109 (2020).
pubmed: 33160249
doi: 10.1016/j.sbi.2020.10.007
pmcid: 8096640
Debrincat, M. A. et al. Ankyrin repeat and suppressors of cytokine signaling box protein asb-9 targets creatine kinase B for degradation. J. Biol. Chem. 282, 4728–4737 (2007).
pubmed: 17148442
doi: 10.1074/jbc.M609164200
Thomas, J. C., Matak-Vinkovic, D., Van Molle, I. & Ciulli, A. Multimeric complexes among ankyrin-repeat and SOCS-box protein 9 (ASB9), ElonginBC, and Cullin 5: insights into the structure and assembly of ECS-type cullin-RING E3 ubiquitin ligases. Biochemistry 52, 5236–5246 (2013).
pubmed: 23837592
doi: 10.1021/bi400758h
Scott, D. C. et al. Two distinct types of E3 ligases work in unison to regulate substrate ubiquitylation. Cell 166, 1198–1214 e1124 (2016).
pubmed: 27565346
pmcid: 5091668
doi: 10.1016/j.cell.2016.07.027
Baek, K. et al. NEDD8 nucleates a multivalent cullin-RING-UBE2D ubiquitin ligation assembly. Nature 578, 461–466 (2020).
pubmed: 32051583
pmcid: 7050210
doi: 10.1038/s41586-020-2000-y
Plechanovova, A., Jaffray, E. G., Tatham, M. H., Naismith, J. H. & Hay, R. T. Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis. Nature 489, 115–120 (2012).
pubmed: 22842904
pmcid: 3442243
doi: 10.1038/nature11376
Pruneda, J. N. et al. Structure of an E3:E2 approximately Ub complex reveals an allosteric mechanism shared among RING/U-box ligases. Mol. Cell 47, 933–942 (2012).
pubmed: 22885007
pmcid: 3462262
doi: 10.1016/j.molcel.2012.07.001
Dou, H., Buetow, L., Sibbet, G. J., Cameron, K. & Huang, D. T. BIRC7-E2 ubiquitin conjugate structure reveals the mechanism of ubiquitin transfer by a RING dimer. Nat. Struct. Mol. Biol. 19, 876–883 (2012).
pubmed: 22902369
doi: 10.1038/nsmb.2379
Kelsall, I. R. et al. TRIAD1 and HHARI bind to and are activated by distinct neddylated Cullin-RING ligase complexes. EMBO J. 32, 2848–2860 (2013).
pubmed: 24076655
pmcid: 3817463
doi: 10.1038/emboj.2013.209
Lumpkin, R. J., Baker, R. W., Leschziner, A. E. & Komives, E. A. Structure and dynamics of the ASB9 CUL-RING E3 Ligase. Nat. Commun. 11, 2866 (2020).
pubmed: 32513959
pmcid: 7280518
doi: 10.1038/s41467-020-16499-9
Horn-Ghetko, D. et al. Ubiquitin ligation to F-box protein targets by SCF-RBR E3–E3 super-assembly. Nature 590, 671–676 (2021).
pubmed: 33536622
pmcid: 7904520
doi: 10.1038/s41586-021-03197-9
Chaugule, V. K. et al. Autoregulation of Parkin activity through its ubiquitin-like domain. EMBO J. 30, 2853–2867 (2011).
pubmed: 21694720
pmcid: 3160258
doi: 10.1038/emboj.2011.204
Duda, D. M. et al. Structure of HHARI, a RING-IBR-RING ubiquitin ligase: autoinhibition of an Ariadne-family E3 and insights into ligation mechanism. Structure 21, 1030–1041 (2013).
pubmed: 23707686
pmcid: 3747818
doi: 10.1016/j.str.2013.04.019
Wauer, T. & Komander, D. Structure of the human Parkin ligase domain in an autoinhibited state. EMBO J. https://doi.org/10.1038/emboj.2013.125 (2013).
doi: 10.1038/emboj.2013.125
pubmed: 23727886
pmcid: 3730226
Trempe, J. F. et al. Structure of Parkin reveals mechanisms for ubiquitin ligase activation. Science 340, 1451–1455 (2013).
pubmed: 23661642
doi: 10.1126/science.1237908
Riley, B. E. et al. Structure and function of Parkin E3 ubiquitin ligase reveals aspects of RING and HECT ligases. Nat. Commun. 4, 1982 (2013).
pubmed: 23770887
doi: 10.1038/ncomms2982
Liu, Y. & Tan, X. Viral manipulations of the Cullin-RING ubiquitin ligases. Adv. Exp. Med Biol. 1217, 99–110 (2020).
pubmed: 31898224
doi: 10.1007/978-981-15-1025-0_7
Yu, X. et al. Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex. Science 302, 1056–1060 (2003).
pubmed: 14564014
doi: 10.1126/science.1089591
Zhang, W., Du, J., Evans, S. L., Yu, Y. & Yu, X. F. T-cell differentiation factor CBF-beta regulates HIV-1 Vif-mediated evasion of host restriction. Nature 481, 376–379 (2011).
pubmed: 22190036
doi: 10.1038/nature10718
Jager, S. et al. Vif hijacks CBF-beta to degrade APOBEC3G and promote HIV-1 infection. Nature 481, 371–375 (2011).
pubmed: 22190037
pmcid: 3310910
doi: 10.1038/nature10693
Lumpkin, R. J., Ahmad, A. S., Blake, R., Condon, C. J. & Komives, E. A. The mechanism of NEDD8 activation of CUL5 ubiquitin E3 ligases. Mol. Cell Proteomics https://doi.org/10.1074/mcp.RA120.002414 (2020).
Lechtenberg, B. C. et al. Structure of a HOIP/E2~ubiquitin complex reveals RBR E3 ligase mechanism and regulation. Nature 529, 546–550 (2016).
pubmed: 26789245
pmcid: 4856479
doi: 10.1038/nature16511
Condos, T. E. et al. Synergistic recruitment of UbcH7~Ub and phosphorylated Ubl domain triggers parkin activation. EMBO J. https://doi.org/10.15252/embj.2018100014 (2018).
Guo, Y. et al. Structural basis for hijacking CBF-beta and CUL5 E3 ligase complex by HIV-1 Vif. Nature 505, 229–233 (2014).
pubmed: 24402281
doi: 10.1038/nature12884
Binning, J. M., Chesarino, N. M., Emerman, M. & Gross, J. D. Structural basis for a species-specific determinant of an SIV Vif protein toward hominid APOBEC3G antagonism. Cell Host Microbe 26, 739–747 e734 (2019).
pubmed: 31830442
pmcid: 6913891
doi: 10.1016/j.chom.2019.10.014
Hu, Y. et al. Structural basis of antagonism of human APOBEC3F by HIV-1 Vif. Nat. Struct. Mol. Biol. 26, 1176–1183 (2019).
pubmed: 31792451
pmcid: 6899190
doi: 10.1038/s41594-019-0343-6
Kitamura, S. et al. The APOBEC3C crystal structure and the interface for HIV-1 Vif binding. Nat. Struct. Mol. Biol. 19, 1005–1010 (2012).
pubmed: 23001005
doi: 10.1038/nsmb.2378
Sanchez-Garcia, R. et al. DeepEMhancer: a deep learning solution for cryo-EM volume post-processing. Commun. Biol. https://doi.org/10.1038/s42003-021-02399-1 (2021).
Scott, D. C. et al. Structure of a RING E3 trapped in action reveals ligation mechanism for the ubiquitin-like protein NEDD8. Cell 157, 1671–1684 (2014).
pubmed: 24949976
pmcid: 4247792
doi: 10.1016/j.cell.2014.04.037
Wauer, T., Simicek, M., Schubert, A. & Komander, D. Mechanism of phospho-ubiquitin-induced PARKIN activation. Nature 524, 370–374 (2015).
pubmed: 26161729
pmcid: 4984986
doi: 10.1038/nature14879
Kumar, A. et al. Parkin-phosphoubiquitin complex reveals cryptic ubiquitin-binding site required for RBR ligase activity. Nat. Struct. Mol. Biol. 24, 475–483 (2017).
pubmed: 28414322
pmcid: 5420311
doi: 10.1038/nsmb.3400
Gladkova, C., Maslen, S. L., Skehel, J. M. & Komander, D. Mechanism of Parkin activation by PINK1. Nature 559, 410–414 (2018).
pubmed: 29995846
pmcid: 6071873
doi: 10.1038/s41586-018-0224-x
Sauve, V. et al. Mechanism of parkin activation by phosphorylation. Nat. Struct. Mol. Biol. 25, 623–630 (2018).
pubmed: 29967542
doi: 10.1038/s41594-018-0088-7
Dove, K. K. et al. Structural studies of HHARI/UbcH7 approximately Ub reveal unique E2 approximately Ub conformational restriction by RBR RING1. Structure 25, 890–900 e895 (2017).
pubmed: 28552575
pmcid: 5462532
doi: 10.1016/j.str.2017.04.013
Yuan, L., Lv, Z., Atkison, J. H. & Olsen, S. K. Structural insights into the mechanism and E2 specificity of the RBR E3 ubiquitin ligase HHARI. Nat. Commun. 8, 211 (2017).
pubmed: 28790309
pmcid: 5548887
doi: 10.1038/s41467-017-00272-6
Baba, D. et al. Crystal structure of thymine DNA glycosylase conjugated to SUMO-1. Nature 435, 979–982 (2005).
pubmed: 15959518
doi: 10.1038/nature03634
Flick, K. et al. Proteolysis-independent regulation of the transcription factor Met4 by a single Lys 48-linked ubiquitin chain. Nat. Cell Biol. 6, 634–641 (2004).
pubmed: 15208638
doi: 10.1038/ncb1143
Lin, A. E. et al. ARIH2 is essential for embryogenesis, and its hematopoietic deficiency causes lethal activation of the immune system. Nat. Immunol. 14, 27–33 (2013).
pubmed: 23179078
doi: 10.1038/ni.2478
Kabsch, W. XDS. Acta Crystallogr. 66, 125–132 (2010).
Sheldrick, G. M. Experimental phasing with SHELXC/D/E: combining chain tracing with density modification. Acta Crystallogr. 66, 479–485 (2010).
Cowtan, K. The Buccaneer software for automated model building. 1. Tracing protein chains. Acta Crystallogr. 62, 1002–1011 (2006).
doi: 10.1107/S0108767306098266
Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. 60, 2126–2132 (2004).
Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. 66, 213–221 (2010).
Mastronarde, D. N. Automated electron microscope tomography using robust prediction of specimen movements. J. Struct. Biol. 152, 36–51 (2005).
doi: 10.1016/j.jsb.2005.07.007
pubmed: 16182563
Scheres, S. H. Processing of structurally heterogeneous cryo-EM data in RELION. Methods Enzymol. 579, 125–157 (2016).
pubmed: 27572726
doi: 10.1016/bs.mie.2016.04.012
Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331–332 (2017).
pubmed: 28250466
pmcid: 5494038
doi: 10.1038/nmeth.4193
Zhang, K. Gctf: real-time CTF determination and correction. J. Struct. Biol. 193, 1–12 (2016).
pubmed: 26592709
pmcid: 4711343
doi: 10.1016/j.jsb.2015.11.003
Pettersen, E. F. et al. UCSF Chimera–a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).
pubmed: 15264254
doi: 10.1002/jcc.20084