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Mechanistic insight into the allosteric activation of a ubiquitin-conjugating enzyme by RING-type ubiquitin ligases.

Ozkan E, Yu H, Deisenhofer J
Proc Natl Acad Sci U S A 102 18890-5 (2005)
Related entries: 2esk, 2esp, 2esq

Cited: 130 times
EuropePMC logo PMID: 16365295

Abstract

Ubiquitin-conjugating enzymes (E2s) collaborate with the ubiquitin-activating enzyme (E1) and ubiquitin ligases (E3s) to attach ubiquitin to target proteins. RING-containing E3s simultaneously bind to E2s and substrates, bringing them into close proximity and thus facilitating ubiquitination. We show herein that, although the E3-binding site on the human E2 UbcH5b is distant from its active site, two RING-type minimal E3 modules lacking substrate-binding functions greatly stimulate the rate of ubiquitin release from the UbcH5b-ubiquitin thioester. Using statistical coupling analysis and mutagenesis, we identify and characterize clusters of coevolving and functionally linked residues within UbcH5b that span its E3-binding and active sites. Several UbcH5b mutants are defective in their stimulation by E3s despite their abilities to bind to these E3s, to form ubiquitin thioesters, and to release ubiquitin at a basal rate. One such mutation, I37A, is distant from both the active site and the E3-binding site of UbcH5b. Our studies reveal structural determinants for communication between distal functional sites of E2s and suggest that RING-type E3s activate E2s allosterically.

Articles - 2eso mentioned but not cited (3)

  1. Mechanistic insight into the allosteric activation of a ubiquitin-conjugating enzyme by RING-type ubiquitin ligases. Ozkan E, Yu H, Deisenhofer J. Proc Natl Acad Sci U S A 102 18890-18895 (2005)
  2. Insights into Ubiquitination from the Unique Clamp-like Binding of the RING E3 AO7 to the E2 UbcH5B. Li S, Liang YH, Mariano J, Metzger MB, Stringer DK, Hristova VA, Li J, Randazzo PA, Tsai YC, Ji X, Weissman AM. J Biol Chem 290 30225-30239 (2015)
  3. SAMPLEX: automatic mapping of perturbed and unperturbed regions of proteins and complexes. Krzeminski M, Loth K, Boelens R, Bonvin AM. BMC Bioinformatics 11 51 (2010)


Reviews citing this publication (37)

  1. RING domain E3 ubiquitin ligases. Deshaies RJ, Joazeiro CA. Annu Rev Biochem 78 399-434 (2009)
  2. Modification of proteins by ubiquitin and ubiquitin-like proteins. Kerscher O, Felberbaum R, Hochstrasser M. Annu Rev Cell Dev Biol 22 159-180 (2006)
  3. Building ubiquitin chains: E2 enzymes at work. Ye Y, Rape M. Nat Rev Mol Cell Biol 10 755-764 (2009)
  4. Ubiquitin Ligases: Structure, Function, and Regulation. Zheng N, Shabek N. Annu Rev Biochem 86 129-157 (2017)
  5. HECT and RING finger families of E3 ubiquitin ligases at a glance. Metzger MB, Hristova VA, Weissman AM. J Cell Sci 125 531-537 (2012)
  6. New insights into ubiquitin E3 ligase mechanism. Berndsen CE, Wolberger C. Nat Struct Mol Biol 21 301-307 (2014)
  7. RING-type E3 ligases: master manipulators of E2 ubiquitin-conjugating enzymes and ubiquitination. Metzger MB, Pruneda JN, Klevit RE, Weissman AM. Biochim Biophys Acta 1843 47-60 (2014)
  8. The ubiquitin-proteasome system of Saccharomyces cerevisiae. Finley D, Ulrich HD, Sommer T, Kaiser P. Genetics 192 319-360 (2012)
  9. Structural insights into the catalysis and regulation of E3 ubiquitin ligases. Buetow L, Huang DT. Nat Rev Mol Cell Biol 17 626-642 (2016)
  10. Protein allostery, signal transmission and dynamics: a classification scheme of allosteric mechanisms. Tsai CJ, Del Sol A, Nussinov R. Mol Biosyst 5 207-216 (2009)
  11. Governance of endocytic trafficking and signaling by reversible ubiquitylation. Clague MJ, Liu H, Urbé S. Dev Cell 23 457-467 (2012)
  12. Protein monoubiquitination and polyubiquitination generate structural diversity to control distinct biological processes. Sadowski M, Suryadinata R, Tan AR, Roesley SN, Sarcevic B. IUBMB Life 64 136-142 (2012)
  13. Structural and functional insights to ubiquitin-like protein conjugation. Streich FC, Lima CD. Annu Rev Biophys 43 357-379 (2014)
  14. Advancing targeted protein degradation for cancer therapy. Dale B, Cheng M, Park KS, Kaniskan HÜ, Xiong Y, Jin J. Nat Rev Cancer 21 638-654 (2021)
  15. Therapeutic strategies within the ubiquitin proteasome system. Eldridge AG, O'Brien T. Cell Death Differ 17 4-13 (2010)
  16. Following Ariadne's thread: a new perspective on RBR ubiquitin ligases. Wenzel DM, Klevit RE. BMC Biol 10 24 (2012)
  17. The multiple layers of ubiquitin-dependent cell cycle control. Wickliffe K, Williamson A, Jin L, Rape M. Chem Rev 109 1537-1548 (2009)
  18. Assembling the building blocks: structure and function of inhibitor of apoptosis proteins. Mace PD, Shirley S, Day CL. Cell Death Differ 17 46-53 (2010)
  19. Development of inhibitors in the ubiquitination cascade. Zhang W, Sidhu SS. FEBS Lett 588 356-367 (2014)
  20. Ubiquitination of substrates by esterification. Wang X, Herr RA, Hansen TH. Traffic 13 19-24 (2012)
  21. Deubiquitinases in cancer. Wei R, Liu X, Yu W, Yang T, Cai W, Liu J, Huang X, Xu GT, Zhao S, Yang J, Liu S. Oncotarget 6 12872-12889 (2015)
  22. The MDM2 gene family. Mendoza M, Mandani G, Momand J. Biomol Concepts 5 9-19 (2014)
  23. A broad view of scaffolding suggests that scaffolding proteins can actively control regulation and signaling of multienzyme complexes through allostery. Nussinov R, Ma B, Tsai CJ. Biochim Biophys Acta 1834 820-829 (2013)
  24. Emerging drug development technologies targeting ubiquitination for cancer therapeutics. Veggiani G, Gerpe MCR, Sidhu SS, Zhang W. Pharmacol Ther 199 139-154 (2019)
  25. Emerging computational approaches for the study of protein allostery. Collier G, Ortiz V. Arch Biochem Biophys 538 6-15 (2013)
  26. The Ubiquitin Conjugating Enzyme: An Important Ubiquitin Transfer Platform in Ubiquitin-Proteasome System. Liu W, Tang X, Qi X, Fu X, Ghimire S, Ma R, Li S, Zhang N, Si H. Int J Mol Sci 21 E2894 (2020)
  27. RING-Domain E3 Ligase-Mediated Host-Virus Interactions: Orchestrating Immune Responses by the Host and Antagonizing Immune Defense by Viruses. Zhang Y, Li LF, Munir M, Munir M, Qiu HJ. Front Immunol 9 1083 (2018)
  28. Mechanisms of ubiquitin transfer by the anaphase-promoting complex. Matyskiela ME, Rodrigo-Brenni MC, Morgan DO. J Biol 8 92 (2009)
  29. The role of allostery in the ubiquitin-proteasome system. Liu J, Nussinov R. Crit Rev Biochem Mol Biol 48 89-97 (2013)
  30. 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)
  31. Emerging roles of HECT-type E3 ubiquitin ligases in autophagy regulation. Melino G, Cecconi F, Pelicci PG, Mak TW, Bernassola F. Mol Oncol 13 2033-2048 (2019)
  32. IAPS and ubiquitylation. Feltham R, Khan N, Silke J. IUBMB Life 64 411-418 (2012)
  33. The Role of Conformational Dynamics in the Recognition and Regulation of Ubiquitination. Khago D, Fucci IJ, Byrd RA. Molecules 25 E5933 (2020)
  34. The emerging roles of E3 ubiquitin ligases in ovarian cancer chemoresistance. Meng Y, Qiu L, Zhang S, Han J. Cancer Drug Resist 4 365-381 (2021)
  35. The Role of Ubiquitination and SUMOylation in Telomere Biology. Zalzman M, Meltzer WA, Portney BA, Brown RA, Gupta A. Curr Issues Mol Biol 35 85-98 (2020)
  36. Using protein motion to read, write, and erase ubiquitin signals. Phillips AH, Corn JE. J Biol Chem 290 26437-26444 (2015)
  37. The E3 Ligases in Cervical Cancer and Endometrial Cancer. Zhai F, Wang J, Yang W, Ye M, Jin X. Cancers (Basel) 14 5354 (2022)

Articles citing this publication (90)

  1. UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Wenzel DM, Lissounov A, Brzovic PS, Klevit RE. Nature 474 105-108 (2011)
  2. Multimodal activation of the ubiquitin ligase SCF by Nedd8 conjugation. Saha A, Deshaies RJ. Mol Cell 32 21-31 (2008)
  3. BIRC7-E2 ubiquitin conjugate structure reveals the mechanism of ubiquitin transfer by a RING dimer. Dou H, Buetow L, Sibbet GJ, Cameron K, Huang DT. Nat Struct Mol Biol 19 876-883 (2012)
  4. Autoregulation of Parkin activity through its ubiquitin-like domain. Chaugule VK, Burchell L, Barber KR, Sidhu A, Leslie SJ, Shaw GS, Walden H. EMBO J 30 2853-2867 (2011)
  5. Structure of an E3:E2~Ub complex reveals an allosteric mechanism shared among RING/U-box ligases. Pruneda JN, Littlefield PJ, Soss SE, Nordquist KA, Chazin WJ, Brzovic PS, Klevit RE. Mol Cell 47 933-942 (2012)
  6. Structure of the MDM2/MDMX RING domain heterodimer reveals dimerization is required for their ubiquitylation in trans. Linke K, Mace PD, Smith CA, Vaux DL, Silke J, Day CL. Cell Death Differ 15 841-848 (2008)
  7. Sequential E2s drive polyubiquitin chain assembly on APC targets. Rodrigo-Brenni MC, Morgan DO. Cell 130 127-139 (2007)
  8. Insights into ubiquitin transfer cascades from a structure of a UbcH5B approximately ubiquitin-HECT(NEDD4L) complex. Kamadurai HB, Kamadurai HB, Souphron J, Scott DC, Duda DM, Miller DJ, Stringer D, Piper RC, Schulman BA. Mol Cell 36 1095-1102 (2009)
  9. Structural mechanisms underlying posttranslational modification by ubiquitin-like proteins. Dye BT, Schulman BA. Annu Rev Biophys Biomol Struct 36 131-150 (2007)
  10. Herpes simplex virus 1 infection induces activation and subsequent inhibition of the IFI16 and NLRP3 inflammasomes. Johnson KE, Chikoti L, Chandran B. J Virol 87 5005-5018 (2013)
  11. An allosteric inhibitor of the human Cdc34 ubiquitin-conjugating enzyme. Ceccarelli DF, Tang X, Pelletier B, Orlicky S, Xie W, Plantevin V, Neculai D, Chou YC, Ogunjimi A, Al-Hakim A, Varelas X, Koszela J, Wasney GA, Vedadi M, Dhe-Paganon S, Cox S, Xu S, Lopez-Girona A, Mercurio F, Wrana J, Durocher D, Meloche S, Webb DR, Tyers M, Sicheri F. Cell 145 1075-1087 (2011)
  12. Atomic structure of the APC/C and its mechanism of protein ubiquitination. Chang L, Zhang Z, Yang J, McLaughlin SH, Barford D. Nature 522 450-454 (2015)
  13. OTUB1 co-opts Lys48-linked ubiquitin recognition to suppress E2 enzyme function. Juang YC, Landry MC, Sanches M, Vittal V, Leung CC, Ceccarelli DF, Mateo AR, Pruneda JN, Mao DY, Szilard RK, Orlicky S, Munro M, Brzovic PS, Klevit RE, Sicheri F, Durocher D. Mol Cell 45 384-397 (2012)
  14. Allosteric activation of E2-RING finger-mediated ubiquitylation by a structurally defined specific E2-binding region of gp78. Das R, Mariano J, Tsai YC, Kalathur RC, Kalathur RC, Kostova Z, Li J, Tarasov SG, McFeeters RL, Altieri AS, Ji X, Byrd RA, Weissman AM. Mol Cell 34 674-685 (2009)
  15. Analysis of the human E2 ubiquitin conjugating enzyme protein interaction network. Markson G, Kiel C, Hyde R, Brown S, Charalabous P, Bremm A, Semple J, Woodsmith J, Duley S, Salehi-Ashtiani K, Vidal M, Komander D, Serrano L, Lehner P, Sanderson CM. Genome Res 19 1905-1911 (2009)
  16. Mechanism of p53 stabilization by ATM after DNA damage. Cheng Q, Chen J. Cell Cycle 9 472-478 (2010)
  17. PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection. Zhang Y, Mao D, Roswit WT, Jin X, Patel AC, Patel DA, Agapov E, Wang Z, Tidwell RM, Atkinson JJ, Huang G, McCarthy R, Yu J, Yun NE, Paessler S, Lawson TG, Omattage NS, Brett TJ, Holtzman MJ. Nat Immunol 16 1215-1227 (2015)
  18. A comprehensive framework of E2-RING E3 interactions of the human ubiquitin-proteasome system. van Wijk SJ, de Vries SJ, Kemmeren P, Huang A, Boelens R, Bonvin AM, Timmers HT. Mol Syst Biol 5 295 (2009)
  19. What was the set of ubiquitin and ubiquitin-like conjugating enzymes in the eukaryote common ancestor? Michelle C, Vourc'h P, Mignon L, Andres CR. J Mol Evol 68 616-628 (2009)
  20. NEDD8 nucleates a multivalent cullin-RING-UBE2D ubiquitin ligation assembly. Baek K, Krist DT, Prabu JR, Hill S, Klügel M, Neumaier LM, von Gronau S, Kleiger G, Schulman BA. Nature 578 461-466 (2020)
  21. Ubiquitin in motion: structural studies of the ubiquitin-conjugating enzyme∼ubiquitin conjugate. Pruneda JN, Stoll KE, Bolton LJ, Brzovic PS, Klevit RE. Biochemistry 50 1624-1633 (2011)
  22. Solution structure of the Hdm2 C2H2C4 RING, a domain critical for ubiquitination of p53. Kostic M, Matt T, Martinez-Yamout MA, Dyson HJ, Wright PE. J Mol Biol 363 433-450 (2006)
  23. Activity-enhancing mutations in an E3 ubiquitin ligase identified by high-throughput mutagenesis. Starita LM, Pruneda JN, Lo RS, Fowler DM, Kim HJ, Hiatt JB, Shendure J, Brzovic PS, Fields S, Klevit RE. Proc Natl Acad Sci U S A 110 E1263-72 (2013)
  24. Smac mimetics activate the E3 ligase activity of cIAP1 protein by promoting RING domain dimerization. Feltham R, Bettjeman B, Budhidarmo R, Mace PD, Shirley S, Condon SM, Chunduru SK, McKinlay MA, Vaux DL, Silke J, Day CL. J Biol Chem 286 17015-17028 (2011)
  25. Structure of a HOIP/E2~ubiquitin complex reveals RBR E3 ligase mechanism and regulation. Lechtenberg BC, Rajput A, Sanishvili R, Dobaczewska MK, Ware CF, Mace PD, Riedl SJ. Nature 529 546-550 (2016)
  26. The unique N terminus of the UbcH10 E2 enzyme controls the threshold for APC activation and enhances checkpoint regulation of the APC. Summers MK, Pan B, Mukhyala K, Jackson PK. Mol Cell 31 544-556 (2008)
  27. Essentiality of a non-RING element in priming donor ubiquitin for catalysis by a monomeric E3. Dou H, Buetow L, Sibbet GJ, Cameron K, Huang DT. Nat Struct Mol Biol 20 982-986 (2013)
  28. A dual E3 mechanism for Rub1 ligation to Cdc53. Scott DC, Monda JK, Grace CR, Duda DM, Kriwacki RW, Kurz T, Schulman BA. Mol Cell 39 784-796 (2010)
  29. Mechanistic insights into active site-associated polyubiquitination by the ubiquitin-conjugating enzyme Ube2g2. Li W, Tu D, Li L, Wollert T, Ghirlando R, Brunger AT, Ye Y. Proc Natl Acad Sci U S A 106 3722-3727 (2009)
  30. Activation of a primed RING E3-E2-ubiquitin complex by non-covalent ubiquitin. Buetow L, Gabrielsen M, Anthony NG, Dou H, Patel A, Aitkenhead H, Sibbet GJ, Smith BO, Huang DT. Mol Cell 58 297-310 (2015)
  31. Catalysis of lysine 48-specific ubiquitin chain assembly by residues in E2 and ubiquitin. Rodrigo-Brenni MC, Foster SA, Morgan DO. Mol Cell 39 548-559 (2010)
  32. RING domain dimerization is essential for RNF4 function. Liew CW, Sun H, Hunter T, Day CL. Biochem J 431 23-29 (2010)
  33. A structurally unique E2-binding domain activates ubiquitination by the ERAD E2, Ubc7p, through multiple mechanisms. Metzger MB, Liang YH, Das R, Mariano J, Li S, Li J, Kostova Z, Byrd RA, Ji X, Weissman AM. Mol Cell 50 516-527 (2013)
  34. Structural insights into the conformation and oligomerization of E2~ubiquitin conjugates. Page RC, Pruneda JN, Amick J, Klevit RE, Misra S. Biochemistry 51 4175-4187 (2012)
  35. The IDOL-UBE2D complex mediates sterol-dependent degradation of the LDL receptor. Zhang L, Fairall L, Goult BT, Calkin AC, Hong C, Millard CJ, Tontonoz P, Schwabe JW. Genes Dev 25 1262-1274 (2011)
  36. Hetero-oligomerization with MdmX rescues the ubiquitin/Nedd8 ligase activity of RING finger mutants of Mdm2. Singh RK, Iyappan S, Scheffner M. J Biol Chem 282 10901-10907 (2007)
  37. A conserved asparagine has a structural role in ubiquitin-conjugating enzymes. Berndsen CE, Wiener R, Yu IW, Ringel AE, Wolberger C. Nat Chem Biol 9 154-156 (2013)
  38. CAT tails drive degradation of stalled polypeptides on and off the ribosome. Sitron CS, Brandman O. Nat Struct Mol Biol 26 450-459 (2019)
  39. The mechanism of ubiquitination in the cullin-RING E3 ligase machinery: conformational control of substrate orientation. Liu J, Nussinov R. PLoS Comput Biol 5 e1000527 (2009)
  40. Crystal structures of two bacterial HECT-like E3 ligases in complex with a human E2 reveal atomic details of pathogen-host interactions. Lin DY, Diao J, Chen J. Proc Natl Acad Sci U S A 109 1925-1930 (2012)
  41. Activation of UbcH5c~Ub is the result of a shift in interdomain motions of the conjugate bound to U-box E3 ligase E4B. Soss SE, Klevit RE, Chazin WJ. Biochemistry 52 2991-2999 (2013)
  42. An automated approach to network features of protein structure ensembles. Bhattacharyya M, Bhat CR, Vishveshwara S. Protein Sci 22 1399-1416 (2013)
  43. Molecular basis for the association of human E4B U box ubiquitin ligase with E2-conjugating enzymes UbcH5c and Ubc4. Benirschke RC, Thompson JR, Nominé Y, Wasielewski E, Juranić N, Macura S, Hatakeyama S, Nakayama KI, Botuyan MV, Mer G. Structure 18 955-965 (2010)
  44. Synthesis of free and proliferating cell nuclear antigen-bound polyubiquitin chains by the RING E3 ubiquitin ligase Rad5. Carlile CM, Pickart CM, Matunis MJ, Cohen RE. J Biol Chem 284 29326-29334 (2009)
  45. E2-c-Cbl recognition is necessary but not sufficient for ubiquitination activity. Huang A, de Jong RN, Wienk H, Winkler GS, Timmers HT, Boelens R. J Mol Biol 385 507-519 (2009)
  46. The N terminus of Cbl-c regulates ubiquitin ligase activity by modulating affinity for the ubiquitin-conjugating enzyme. Ryan PE, Sivadasan-Nair N, Nau MM, Nicholas S, Lipkowitz S. J Biol Chem 285 23687-23698 (2010)
  47. Turning the RING domain protein MdmX into an active ubiquitin-protein ligase. Iyappan S, Wollscheid HP, Rojas-Fernandez A, Marquardt A, Tang HC, Singh RK, Scheffner M. J Biol Chem 285 33065-33072 (2010)
  48. Engineering a ubiquitin ligase reveals conformational flexibility required for ubiquitin transfer. Qian SB, Waldron L, Choudhary N, Klevit RE, Chazin WJ, Patterson C. J Biol Chem 284 26797-26802 (2009)
  49. DNA-binding regulates site-specific ubiquitination of IRF-1. Landré V, Pion E, Narayan V, Xirodimas DP, Ball KL. Biochem J 449 707-717 (2013)
  50. UBE2W interacts with FANCL and regulates the monoubiquitination of Fanconi anemia protein FANCD2. Zhang Y, Zhou X, Zhao L, Li C, Zhu H, Xu L, Shan L, Liao X, Guo Z, Huang P. Mol Cells 31 113-122 (2011)
  51. Rbx1 flexible linker facilitates cullin-RING ligase function before neddylation and after deneddylation. Liu J, Nussinov R. Biophys J 99 736-744 (2010)
  52. Role of a non-canonical surface of Rad6 in ubiquitin conjugating activity. Kumar P, Kumar P, Magala P, Geiger-Schuller KR, Majumdar A, Tolman JR, Wolberger C. Nucleic Acids Res 43 9039-9050 (2015)
  53. The essential Ubc4/Ubc5 function in yeast is HECT E3-dependent, and RING E3-dependent pathways require only monoubiquitin transfer by Ubc4. Stoll KE, Brzovic PS, Davis TN, Klevit RE. J Biol Chem 286 15165-15170 (2011)
  54. Genome-Wide Identification, Phylogenetic and Expression Analyses of the Ubiquitin-Conjugating Enzyme Gene Family in Maize. Jue D, Sang X, Lu S, Dong C, Zhao Q, Chen H, Jia L. PLoS One 10 e0143488 (2015)
  55. Functional analysis and consequences of Mdm2 E3 ligase inhibition in human tumor cells. Wade M, Li YC, Matani AS, Braun SM, Milanesi F, Rodewald LW, Wahl GM. Oncogene 31 4789-4797 (2012)
  56. Porcine MKRN1 Modulates the Replication and Pathogenesis of Porcine Circovirus Type 2 by Inducing Capsid Protein Ubiquitination and Degradation. Wang T, Du Q, Wu X, Niu Y, Guan L, Wang Z, Zhao X, Liu SL, Tong D, Huang Y. J Virol 92 e00100-18 (2018)
  57. 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)
  58. Paths of long-range communication in the E2 enzymes of family 3: a molecular dynamics investigation. Papaleo E, Lindorff-Larsen K, De Gioia L. Phys Chem Chem Phys 14 12515-12525 (2012)
  59. A nanobody that recognizes a 14-residue peptide epitope in the E2 ubiquitin-conjugating enzyme UBC6e modulates its activity. Ling J, Cheloha RW, McCaul N, Sun ZJ, Wagner G, Ploegh HL. Mol Immunol 114 513-523 (2019)
  60. Emi2-mediated inhibition of E2-substrate ubiquitin transfer by the anaphase-promoting complex/cyclosome through a D-box-independent mechanism. Tang W, Wu JQ, Chen C, Yang CS, Guo JY, Freel CD, Kornbluth S. Mol Biol Cell 21 2589-2597 (2010)
  61. Scaffold Protein SLP-76 Primes PLCγ1 for Activation by ITK-Mediated Phosphorylation. Devkota S, Joseph RE, Min L, Bruce Fulton D, Andreotti AH. J Mol Biol 427 2734-2747 (2015)
  62. RING E3-Catalyzed E2 Self-Ubiquitination Attenuates the Activity of Ube2E Ubiquitin-Conjugating Enzymes. Banka PA, Behera AP, Sarkar S, Datta AB. J Mol Biol 427 2290-2304 (2015)
  63. Stabilization of an E3 ligase-E2-ubiquitin complex increases cell surface MHC class I expression. Duncan LM, Nathan JA, Lehner PJ. J Immunol 184 6978-6985 (2010)
  64. E3 ubiquitin-protein ligase TRIM21-mediated lysine capture by UBE2E1 reveals substrate-targeting mode of a ubiquitin-conjugating E2. Anandapadamanaban M, Kyriakidis NC, Csizmók V, Wallenhammar A, Espinosa AC, Ahlner A, Round AR, Trewhella J, Moche M, Wahren-Herlenius M, Sunnerhagen M. J Biol Chem 294 11404-11419 (2019)
  65. Genome-wide identification and expression analysis of E2 ubiquitin-conjugating enzymes in tomato. Sharma B, Bhatt TK. Sci Rep 7 8613 (2017)
  66. Label free fragment screening using surface plasmon resonance as a tool for fragment finding - analyzing parkin, a difficult CNS target. Regnström K, Yan J, Nguyen L, Callaway K, Yang Y, Diep L, Xing W, Adhikari A, Beroza P, Hom RK, Riley B, Rudolph D, Jobling MF, Baker J, Johnston J, Konradi A, Bova MP, Artis DR. PLoS One 8 e66879 (2013)
  67. Protein-Protein Interactions Modulate the Docking-Dependent E3-Ubiquitin Ligase Activity of Carboxy-Terminus of Hsc70-Interacting Protein (CHIP). Narayan V, Landré V, Ning J, Hernychova L, Muller P, Verma C, Walkinshaw MD, Blackburn EA, Ball KL. Mol Cell Proteomics 14 2973-2987 (2015)
  68. Structural determinants of ubiquitin conjugation in Entamoeba histolytica. Bosch DE, Siderovski DP. J Biol Chem 288 2290-2302 (2013)
  69. Force-clamp spectroscopy detects residue co-evolution in enzyme catalysis. Perez-Jimenez R, Wiita AP, Rodriguez-Larrea D, Kosuri P, Gavira JA, Sanchez-Ruiz JM, Fernandez JM. J Biol Chem 283 27121-27129 (2008)
  70. Mutant p53 Sequestration of the MDM2 Acidic Domain Inhibits E3 Ligase Activity. Yang L, Song T, Cheng Q, Chen L, Chen J. Mol Cell Biol 39 e00375-18 (2019)
  71. A C2HC zinc finger is essential for the RING-E2 interaction of the ubiquitin ligase RNF125. Bijlmakers MJ, Teixeira JM, Boer R, Mayzel M, Puig-Sàrries P, Karlsson G, Coll M, Pons M, Crosas B. Sci Rep 6 29232 (2016)
  72. A site-directed mutagenesis study of the MdmX RING domain. Egorova O, Mis M, Sheng Y. Biochem Biophys Res Commun 447 696-701 (2014)
  73. Correlation analysis for protein evolutionary family based on amino acid position mutations and application in PDZ domain. Du QS, Wang CH, Liao SM, Huang RB. PLoS One 5 e13207 (2010)
  74. Genome-wide identification and expression analysis of the E2 gene family in potato. Liu W, Tang X, Zhu X, Qi X, Zhang N, Si H. Mol Biol Rep 46 777-791 (2019)
  75. 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)
  76. Atomic-Resolution Structures of the APC/C Subunits Apc4 and the Apc5 N-Terminal Domain. Cronin NB, Yang J, Zhang Z, Kulkarni K, Chang L, Yamano H, Barford D. J Mol Biol 427 3300-3315 (2015)
  77. Fission yeast Dma1 requires RING domain dimerization for its ubiquitin ligase activity and mitotic checkpoint function. Johnson AE, Collier SE, Ohi MD, Gould KL. J Biol Chem 287 25741-25748 (2012)
  78. HAX1 regulates E3 ubiquitin ligase activity of cIAPs by promoting their dimerization. Choi JS, Park BC, Chi SW, Bae KH, Kim S, Cho S, Son WC, Myung PK, Kim JH, Park SG. Oncotarget 5 10084-10099 (2014)
  79. Molecular Simulation Elaborating the Mechanism of 1β-Hydroxy Alantolactone Inhibiting Ubiquitin-Conjugating Enzyme UbcH5s. Xu Y, Meng X. Sci Rep 10 141 (2020)
  80. An E2 accessory domain increases affinity for the anaphase-promoting complex and ensures E2 competition. Girard JR, Tenthorey JL, Morgan DO. J Biol Chem 290 24614-24625 (2015)
  81. Functional conservation and divergence of the helix-turn-helix motif of E2 ubiquitin-conjugating enzymes. Welsh KA, Bolhuis DL, Nederstigt AE, Boyer J, Temple BRS, Bonacci T, Gu L, Ordureau A, Harper JW, Steimel JP, Zhang Q, Emanuele MJ, Harrison JS, Brown NG. EMBO J 41 e108823 (2022)
  82. Proteome-wide identification and functional analysis of ubiquitinated proteins in peach leaves. Song Y, Shi X, Zou Y, Guo J, Huo N, Chen S, Zhao C, Li H, Wu G, Peng Y. Sci Rep 10 2447 (2020)
  83. The RING domain of mitochondrial E3 ubiquitin ligase 1 and its complex with Ube2D2: crystallization and X-ray diffraction. Lee SO, Lee CK, Ryu KS, Chi SW. Acta Crystallogr F Struct Biol Commun 76 1-7 (2020)
  84. Comment (G2)BRinging an E2 to E3. Wang J, Schulman BA. Structure 17 916-917 (2009)
  85. Drosophila morgue associates with SkpA and polyubiquitin in vivo. Zhou Y, Wang Y, Schreader BA, Nambu JR. PLoS One 8 e74860 (2013)
  86. Further insights into the ubiquitin pathway: understanding the scarlet letter code. Pastore A. Structure 18 891-892 (2010)
  87. An alternative allosteric pathway in thermophilic methylglyoxal synthase. Atabakhshi-Kashi M, Mohammadi M, Mirhassani R, Dabirmanesh B, Sajedi RH, Khajeh K. Int J Biol Macromol 93 526-533 (2016)
  88. Genome-wide characterization of ubiquitin-conjugating enzyme gene family explores its genetic effects on the oil content and yield of Brassica napus. Yao S, Xie M, Hu M, Cui X, Wu H, Li X, Hu P, Tong C, Yu X. Front Plant Sci 14 1118339 (2023)
  89. Sesquiterpene Lactones Potentiate Olaparib-Induced DNA Damage in p53 Wildtype Cancer Cells. Osborne HC, Larrosa I, Schmidt CK. Int J Mol Sci 23 1116 (2022)
  90. Structural position correlation analysis (SPCA) for protein family. Du QS, Meng JZ, Wang CH, Long SY, Huang RB. PLoS One 6 e28206 (2011)


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