5aiu › Citations

Structural basis for the RING-catalyzed synthesis of K63-linked ubiquitin chains.

Branigan E, Plechanovová A, Jaffray EG, Naismith JH, Hay RT
Nat Struct Mol Biol 22 597-602 (2015)
Cited: 70 times
EuropePMC logo PMID: 26148049

Abstract

RING E3 ligase-catalyzed formation of K63-linked ubiquitin chains by the Ube2V2-Ubc13 E2 complex is required in many important biological processes. Here we report the structure of the RING-domain dimer of rat RNF4 in complex with a human Ubc13∼Ub conjugate and Ube2V2. The structure has captured Ube2V2 bound to the acceptor (priming) ubiquitin with K63 in a position favorable for attack on the linkage between Ubc13 and the donor (second) ubiquitin held in the active 'folded back' conformation by the RING domain of RNF4. We verified the interfaces identified in the structure by in vitro ubiquitination assays of site-directed mutants. To our knowledge, this represents the first view of synthesis of K63-linked ubiquitin chains in which both substrate ubiquitin and ubiquitin-loaded E2 are juxtaposed to allow E3 ligase-mediated catalysis.

Articles - 5aiu mentioned but not cited (6)

  1. Structural basis for the RING-catalyzed synthesis of K63-linked ubiquitin chains. Branigan E, Plechanovová A, Jaffray EG, Naismith JH, Hay RT. Nat Struct Mol Biol 22 597-602 (2015)
  2. RNF8 E3 Ubiquitin Ligase Stimulates Ubc13 E2 Conjugating Activity That Is Essential for DNA Double Strand Break Signaling and BRCA1 Tumor Suppressor Recruitment. Hodge CD, Ismail IH, Edwards RA, Hura GL, Xiao AT, Tainer JA, Hendzel MJ, Glover JN. J. Biol. Chem. 291 9396-9410 (2016)
  3. The activity of TRAF RING homo- and heterodimers is regulated by zinc finger 1. Middleton AJ, Budhidarmo R, Das A, Zhu J, Foglizzo M, Mace PD, Day CL. Nat Commun 8 1788 (2017)
  4. Ubiquitin transfer by a RING E3 ligase occurs from a closed E2~ubiquitin conformation. Branigan E, Carlos Penedo J, Hay RT. Nat Commun 11 2846 (2020)
  5. Electroacupuncture Treats Myocardial Infarction by Influencing the Regulation of Substance P in the Neurovascular to Modulate PGI2/TXA2 Metabolic Homeostasis via PI3K/AKT Pathway: A Bioinformatics-Based Multiomics and Experimental Study. Zhang P, Wang Y, Xing X, Li H, Wang X, Zhang H, Wang X, Li X, Li Y, Wang Q. Comput Math Methods Med 2022 5367753 (2022)
  6. Mechanistic insights revealed by a UBE2A mutation linked to intellectual disability. de Oliveira JF, do Prado PFV, da Costa SS, Sforça ML, Canateli C, Ranzani AT, Maschietto M, de Oliveira PSL, Otto PA, Klevit RE, Krepischi ACV, Rosenberg C, Franchini KG. Nat. Chem. Biol. 15 62-70 (2019)


Reviews citing this publication (20)

  1. The increasing complexity of the ubiquitin code. Yau R, Rape M. Nat. Cell Biol. 18 579-586 (2016)
  2. Regulation of DNA double-strand break repair by ubiquitin and ubiquitin-like modifiers. Schwertman P, Bekker-Jensen S, Mailand N. Nat. Rev. Mol. Cell Biol. 17 379-394 (2016)
  3. Ubiquitin Ligases: Structure, Function, and Regulation. Zheng N, Shabek N. Annu. Rev. Biochem. 86 129-157 (2017)
  4. Structural insights into the catalysis and regulation of E3 ubiquitin ligases. Buetow L, Huang DT. Nat. Rev. Mol. Cell Biol. 17 626-642 (2016)
  5. E2 enzymes: more than just middle men. Stewart MD, Ritterhoff T, Klevit RE, Brzovic PS. Cell Res. 26 423-440 (2016)
  6. Ubiquitin-like Protein Conjugation: Structures, Chemistry, and Mechanism. Cappadocia L, Lima CD. Chem. Rev. 118 889-918 (2018)
  7. RING-Between-RING E3 Ligases: Emerging Themes amid the Variations. Dove KK, Klevit RE. J. Mol. Biol. 429 3363-3375 (2017)
  8. Ubc13: the Lys63 ubiquitin chain building machine. Hodge CD, Spyracopoulos L, Glover JN. Oncotarget 7 64471-64504 (2016)
  9. Structural mechanisms of HECT-type ubiquitin ligases. Lorenz S. Biol. Chem. 399 127-145 (2018)
  10. SUMO, a small, but powerful, regulator of double-strand break repair. Garvin AJ, Morris JR. Philos. Trans. R. Soc. Lond., B, Biol. Sci. 372 (2017)
  11. SUMO-Targeted Ubiquitin Ligases and Their Functions in Maintaining Genome Stability. Chang YC, Oram MK, Bielinsky AK. Int J Mol Sci 22 5391 (2021)
  12. Molecular Basis for K63-Linked Ubiquitination Processes in Double-Strand DNA Break Repair: A Focus on Kinetics and Dynamics. Lee BL, Singh A, Mark Glover JN, Hendzel MJ, Spyracopoulos L. J Mol Biol 429 3409-3429 (2017)
  13. Noncovalent Ubiquitin Interactions Regulate the Catalytic Activity of Ubiquitin Writers. Wright JD, Mace PD, Day CL. Trends Biochem. Sci. 41 924-937 (2016)
  14. SUMO in the DNA Double-Stranded Break Response: Similarities, Differences, and Cooperation with Ubiquitin. Morris JR, Garvin AJ. J. Mol. Biol. 429 3376-3387 (2017)
  15. Regulation of E2s: A Role for Additional Ubiquitin Binding Sites? Middleton AJ, Wright JD, Day CL. J. Mol. Biol. 429 3430-3440 (2017)
  16. The Role of Conformational Dynamics in the Recognition and Regulation of Ubiquitination. Khago D, Fucci IJ, Byrd RA. Molecules 25 E5933 (2020)
  17. Enzymatic Logic of Ubiquitin Chain Assembly. Deol KK, Lorenz S, Strieter ER. Front Physiol 10 835 (2019)
  18. From seeds to trees: how E2 enzymes grow ubiquitin chains. Middleton AJ, Day CL. Biochem Soc Trans 51 353-362 (2023)
  19. Preserving genome integrity: The vital role of SUMO-targeted ubiquitin ligases. Han J, Mu Y, Huang J. Cell Insight 2 100128 (2023)
  20. Ubiquitylation-Mediated Fine-Tuning of DNA Double-Strand Break Repair. Borsos BN, Majoros H, Pankotai T. Cancers (Basel) 12 (2020)

Articles citing this publication (44)

  1. Dual RING E3 Architectures Regulate Multiubiquitination and Ubiquitin Chain Elongation by APC/C. Brown NG, VanderLinden R, Watson ER, Weissmann F, Ordureau A, Wu KP, Zhang W, Yu S, Mercredi PY, Harrison JS, Davidson IF, Qiao R, Lu Y, Dube P, Brunner MR, Grace CRR, Miller DJ, Haselbach D, Jarvis MA, Yamaguchi M, Yanishevski D, Petzold G, Sidhu SS, Kuhlman B, Kirschner MW, Harper JW, Peters JM, Stark H, Schulman BA. Cell 165 1440-1453 (2016)
  2. Structural basis for catalytic activation by the human ZNF451 SUMO E3 ligase. Cappadocia L, Pichler A, Lima CD. Nat. Struct. Mol. Biol. 22 968-975 (2015)
  3. Molecular insights into RBR E3 ligase ubiquitin transfer mechanisms. Dove KK, Stieglitz B, Duncan ED, Rittinger K, Klevit RE. EMBO Rep. 17 1221-1235 (2016)
  4. Hemi-methylated DNA regulates DNA methylation inheritance through allosteric activation of H3 ubiquitylation by UHRF1. Harrison JS, Cornett EM, Goldfarb D, DaRosa PA, Li ZM, Yan F, Dickson BM, Guo AH, Cantu DV, Kaustov L, Brown PJ, Arrowsmith CH, Erie DA, Major MB, Klevit RE, Krajewski K, Kuhlman B, Strahl BD, Rothbart SB. Elife 5 (2016)
  5. Secondary ubiquitin-RING docking enhances Arkadia and Ark2C E3 ligase activity. Wright JD, Mace PD, Day CL. Nat. Struct. Mol. Biol. 23 45-52 (2016)
  6. Crystal Structure of a Ube2S-Ubiquitin Conjugate. Lorenz S, Bhattacharyya M, Feiler C, Rape M, Kuriyan J. PLoS ONE 11 e0147550 (2016)
  7. RING domains act as both substrate and enzyme in a catalytic arrangement to drive self-anchored ubiquitination. Kiss L, Clift D, Renner N, Neuhaus D, James LC. Nat Commun 12 1220 (2021)
  8. Who with whom: functional coordination of E2 enzymes by RING E3 ligases during poly-ubiquitylation. Lips C, Ritterhoff T, Weber A, Janowska MK, Mustroph M, Sommer T, Klevit RE. EMBO J 39 e104863 (2020)
  9. Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity. Nomura K, Klejnot M, Kowalczyk D, Hock AK, Sibbet GJ, Vousden KH, Huang DT. Nat. Struct. Mol. Biol. 24 578-587 (2017)
  10. Ube2V2 Is a Rosetta Stone Bridging Redox and Ubiquitin Codes, Coordinating DNA Damage Responses. Zhao Y, Long MJC, Wang Y, Zhang S, Aye Y. ACS Cent Sci 4 246-259 (2018)
  11. A non-canonical scaffold-type E3 ligase complex mediates protein UFMylation. Peter JJ, Magnussen HM, DaRosa PA, Millrine D, Matthews SP, Lamoliatte F, Sundaramoorthy R, Kopito RR, Kulathu Y. EMBO J 41 e111015 (2022)
  12. Identification of RNF168 as a PML nuclear body regulator. Shire K, Wong AI, Tatham MH, Anderson OF, Ripsman D, Gulstene S, Moffat J, Hay RT, Frappier L. J. Cell. Sci. 129 580-591 (2016)
  13. Linkage-specific ubiquitin chain formation depends on a lysine hydrocarbon ruler. Liwocha J, Krist DT, van der Heden van Noort GJ, Hansen FM, Truong VH, Karayel O, Purser N, Houston D, Burton N, Bostock MJ, Sattler M, Mann M, Harrison JS, Kleiger G, Ovaa H, Schulman BA. Nat Chem Biol 17 272-279 (2021)
  14. Mechanism of Lysine 48 Selectivity during Polyubiquitin Chain Formation by the Ube2R1/2 Ubiquitin-Conjugating Enzyme. Hill S, Harrison JS, Lewis SM, Kuhlman B, Kleiger G. Mol. Cell. Biol. 36 1720-1732 (2016)
  15. Single-cell transcriptome analysis of human oocyte ageing. Yuan L, Yin P, Yan H, Zhong X, Ren C, Li K, Heng BC, Zhang W, Tong G. J Cell Mol Med (2021)
  16. The UBA domain of conjugating enzyme Ubc1/Ube2K facilitates assembly of K48/K63-branched ubiquitin chains. Pluska L, Jarosch E, Zauber H, Kniss A, Waltho A, Bagola K, von Delbrück M, Löhr F, Schulman BA, Selbach M, Dötsch V, Sommer T. EMBO J 40 e106094 (2021)
  17. Tuning BRCA1 and BARD1 activity to investigate RING ubiquitin ligase mechanisms. Stewart MD, Duncan ED, Coronado E, DaRosa PA, Pruneda JN, Brzovic PS, Klevit RE. Protein Sci. 26 475-483 (2017)
  18. Inhibition of Ubc13-mediated Ubiquitination by GPS2 Regulates Multiple Stages of B Cell Development. Lentucci C, Belkina AC, Cederquist CT, Chan M, Johnson HE, Prasad S, Lopacinski A, Nikolajczyk BS, Monti S, Snyder-Cappione J, Tanasa B, Cardamone MD, Perissi V. J. Biol. Chem. 292 2754-2772 (2017)
  19. Mechanism of ubiquitin transfer promoted by TRAF6. Fu TM, Shen C, Li Q, Zhang P, Wu H. Proc. Natl. Acad. Sci. U.S.A. 115 1783-1788 (2018)
  20. Active Site Gate Dynamics Modulate the Catalytic Activity of the Ubiquitination Enzyme E2-25K. Rout MK, Lee BL, Lin A, Xiao W, Spyracopoulos L. Sci Rep 8 7002 (2018)
  21. Analysis of ubiquitin recognition by the HECT ligase E6AP provides insight into its linkage specificity. Ries LK, Sander B, Deol KK, Letzelter MA, Strieter ER, Lorenz S. J. Biol. Chem. 294 6113-6129 (2019)
  22. Crystal structures of an E1-E2-ubiquitin thioester mimetic reveal molecular mechanisms of transthioesterification. Yuan L, Lv Z, Adams MJ, Olsen SK. Nat Commun 12 2370 (2021)
  23. Lys63-polyubiquitination by the E3 ligase casitas B-lineage lymphoma-b (Cbl-b) modulates peripheral regulatory T cell tolerance in patients with systemic lupus erythematosus. Romo-Tena J, Rajme-López S, Aparicio-Vera L, Alcocer-Varela J, Gómez-Martín D. Clin. Exp. Immunol. 191 42-49 (2018)
  24. Structural and functional asymmetry of RING trimerization controls priming and extension events in TRIM5α autoubiquitylation. Herkules F, Yu CH, Taylor AB, Dougherty V, Weintraub ST, Ivanov DN. Nat Commun 13 7104 (2022)
  25. Structural basis for the Rad6 activation by the Bre1 N-terminal domain. Shi M, Zhao J, Zhang S, Huang W, Li M, Bai X, Zhang W, Zhang K, Chen X, Xiang S. Elife 12 e84157 (2023)
  26. Structural insights into non-covalent ubiquitin activation of the cIAP1-UbcH5B∼ubiquitin complex. Patel A, Sibbet GJ, Huang DT. J. Biol. Chem. 294 1240-1249 (2019)
  27. Structural snapshots along K48-linked ubiquitin chain formation by the HECT E3 UBR5. Hehl LA, Horn-Ghetko D, Prabu JR, Vollrath R, Vu DT, Pérez Berrocal DA, Mulder MPC, van der Heden van Noort GJ, Schulman BA. Nat Chem Biol (2023)
  28. Letter The RING domain of RING Finger 11 (RNF11) protein binds Ubc13 and inhibits formation of polyubiquitin chains. Budhidarmo R, Zhu J, Middleton AJ, Day CL. FEBS Lett. 592 1434-1444 (2018)
  29. The San1 Ubiquitin Ligase Functions Preferentially with Ubiquitin-conjugating Enzyme Ubc1 during Protein Quality Control. Ibarra R, Sandoval D, Fredrickson EK, Gardner RG, Kleiger G. J. Biol. Chem. 291 18778-18790 (2016)
  30. Trivalent RING Assembly on Retroviral Capsids Activates TRIM5 Ubiquitination and Innate Immune Signaling. Fletcher AJ, Vaysburd M, Maslen S, Zeng J, Skehel JM, Towers GJ, James LC. Cell Host Microbe 24 761-775.e6 (2018)
  31. A tri-ionic anchor mechanism drives Ube2N-specific recruitment and K63-chain ubiquitination in TRIM ligases. Kiss L, Zeng J, Dickson CF, Mallery DL, Yang JC, McLaughlin SH, Boland A, Neuhaus D, James LC. Nat Commun 10 4502 (2019)
  32. Analysis of the Zn-Binding Domains of TRIM32, the E3 Ubiquitin Ligase Mutated in Limb Girdle Muscular Dystrophy 2H. Lazzari E, El-Halawany MS, De March M, Valentino F, Cantatore F, Migliore C, Onesti S, Meroni G. Cells 8 (2019)
  33. Antibody RING-Mediated Destruction of Endogenous Proteins. Ibrahim AFM, Shen L, Tatham MH, Dickerson D, Prescott AR, Abidi N, Xirodimas DP, Hay RT. Mol Cell 79 155-166.e9 (2020)
  34. Cryo-EM structures of Uba7 reveal the molecular basis for ISG15 activation and E1-E2 thioester transfer. Afsar M, Liu G, Jia L, Ruben EA, Nayak D, Sayyad Z, Bury PDS, Cano KE, Nayak A, Zhao XR, Shukla A, Sung P, Wasmuth EV, Gack MU, Olsen SK. Nat Commun 14 4786 (2023)
  35. Deamidation disrupts native and transient contacts to weaken the interaction between UBC13 and RING-finger E3 ligases. Mohanty P, Agrata R, Habibullah BI, G S A, Das R. Elife 8 (2019)
  36. FBXL6 governs c-MYC to promote hepatocellular carcinoma through ubiquitination and stabilization of HSP90AA1. Shi W, Feng L, Dong S, Ning Z, Hua Y, Liu L, Chen Z, Meng Z. Cell Commun Signal 18 100 (2020)
  37. Functional 3D architecture in an intrinsically disordered E3 ligase domain facilitates ubiquitin transfer. Murphy P, Xu Y, Rouse SL, Jaffray EG, Plechanovová A, Matthews SJ, Carlos Penedo J, Hay RT. Nat Commun 11 3807 (2020)
  38. HECT domain interaction with ubiquitin binding sites on Tsg101-UEV controls HIV-1 egress, maturation, and infectivity. Nyenhuis DA, Rajasekaran R, Watanabe S, Strub MP, Khan M, Powell M, Carter CA, Tjandra N. J Biol Chem 299 102901 (2023)
  39. Leishmania differentiation requires ubiquitin conjugation mediated by a UBC2-UEV1 E2 complex. Burge RJ, Damianou A, Wilkinson AJ, Rodenko B, Mottram JC. PLoS Pathog 16 e1008784 (2020)
  40. MKP-1 modulates ubiquitination/phosphorylation of TLR signaling. Talreja J, Bauerfeld C, Wang X, Hafner M, Liu Y, Samavati L. Life Sci Alliance 4 e202101137 (2021)
  41. Photocrosslinking Activity-Based Probes for Ubiquitin RING E3 Ligases. Mathur S, Fletcher AJ, Branigan E, Hay RT, Virdee S. Cell Chem Biol 27 74-82.e6 (2020)
  42. Strategies to Trap Enzyme-Substrate Complexes that Mimic Michaelis Intermediates During E3-Mediated Ubiquitin-Like Protein Ligation. Streich FC, Lima CD. Methods Mol. Biol. 1844 169-196 (2018)
  43. Structural insights into the regulation of the human E2∼SUMO conjugate through analysis of its stable mimetic. Goffinont S, Coste F, Prieu-Serandon P, Mance L, Gaudon V, Garnier N, Castaing B, Suskiewicz MJ. J Biol Chem 299 104870 (2023)
  44. Structure of UBE2K-Ub/E3/polyUb reveals mechanisms of K48-linked Ub chain extension. Nakasone MA, Majorek KA, Gabrielsen M, Sibbet GJ, Smith BO, Huang DT. Nat Chem Biol 18 422-431 (2022)


Quick links