4y1h Citations

Assembly and structure of Lys33-linked polyubiquitin reveals distinct conformations.

Abstract

Ubiquitylation regulates a multitude of biological processes and this versatility stems from the ability of ubiquitin (Ub) to form topologically different polymers of eight different linkage types. Whereas some linkages have been studied in detail, other linkage types including Lys33-linked polyUb are poorly understood. In the present study, we identify an enzymatic system for the large-scale assembly of Lys33 chains by combining the HECT (homologous to the E6-AP C-terminus) E3 ligase AREL1 (apoptosis-resistant E3 Ub protein ligase 1) with linkage selective deubiquitinases (DUBs). Moreover, this first characterization of the chain selectivity of AREL1 indicates its preference for assembling Lys33- and Lys11-linked Ub chains. Intriguingly, the crystal structure of Lys33-linked diUb reveals that it adopts a compact conformation very similar to that observed for Lys11-linked diUb. In contrast, crystallographic analysis of Lys33-linked triUb reveals a more extended conformation. These two distinct conformational states of Lys33-linked polyUb may be selectively recognized by Ub-binding domains (UBD) and enzymes of the Ub system. Importantly, our work provides a method to assemble Lys33-linked polyUb that will allow further characterization of this atypical chain type.

Articles - 4y1h mentioned but not cited (1)

  1. Assembly and structure of Lys33-linked polyubiquitin reveals distinct conformations. Kristariyanto YA, Choi SY, Rehman SA, Ritorto MS, Campbell DG, Morrice NA, Toth R, Kulathu Y. Biochem J 467 345-352 (2015)


Reviews citing this publication (14)

  1. Ubiquitin modifications. Swatek KN, Komander D. Cell Res 26 399-422 (2016)
  2. Mechanisms of Deubiquitinase Specificity and Regulation. Mevissen TET, Komander D. Annu Rev Biochem 86 159-192 (2017)
  3. Ubiquitin chain diversity at a glance. Akutsu M, Dikic I, Bremm A. J Cell Sci 129 875-880 (2016)
  4. Substrate specificity of the ubiquitin and Ubl proteases. Ronau JA, Beckmann JF, Hochstrasser M. Cell Res 26 441-456 (2016)
  5. HECT E3 Ligases: A Tale With Multiple Facets. Weber J, Polo S, Maspero E. Front Physiol 10 370 (2019)
  6. Targeting HECT-type E3 ligases - insights from catalysis, regulation and inhibitors. Fajner V, Maspero E, Polo S. FEBS Lett 591 2636-2647 (2017)
  7. Specificity and disease in the ubiquitin system. Chaugule VK, Walden H. Biochem Soc Trans 44 212-227 (2016)
  8. Structure, Dynamics and Function of the 26S Proteasome. Mao Y. Subcell Biochem 96 1-151 (2021)
  9. 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)
  10. E3 Ubiquitin ligase NEDD4 family‑regulatory network in cardiovascular disease. Zhang Y, Qian H, Wu B, You S, Wu S, Lu S, Wang P, Cao L, Zhang N, Sun Y. Int J Biol Sci 16 2727-2740 (2020)
  11. Peeling away the layers of ubiquitin signaling complexities with synthetic ubiquitin-protein conjugates. Pham GH, Strieter ER. Curr Opin Chem Biol 28 57-65 (2015)
  12. Unanchored Ubiquitin Chains, Revisited. Blount JR, Johnson SL, Todi SV. Front Cell Dev Biol 8 582361 (2020)
  13. Chemical ubiquitination for decrypting a cellular code. Stanley M, Virdee S. Biochem J 473 1297-1314 (2016)
  14. Mechanism and Disease Association With a Ubiquitin Conjugating E2 Enzyme: UBE2L3. Zhang X, Huo C, Liu Y, Su R, Zhao Y, Li Y. Front Immunol 13 793610 (2022)

Articles citing this publication (28)

  1. MINDY-1 Is a Member of an Evolutionarily Conserved and Structurally Distinct New Family of Deubiquitinating Enzymes. Abdul Rehman SA, Kristariyanto YA, Choi SY, Nkosi PJ, Weidlich S, Labib K, Hofmann K, Kulathu Y. Mol Cell 63 146-155 (2016)
  2. Binding to serine 65-phosphorylated ubiquitin primes Parkin for optimal PINK1-dependent phosphorylation and activation. Kazlauskaite A, Martínez-Torres RJ, Wilkie S, Kumar A, Peltier J, Gonzalez A, Johnson C, Zhang J, Hope AG, Peggie M, Trost M, van Aalten DM, Alessi DR, Prescott AR, Knebel A, Walden H, Muqit MM. EMBO Rep 16 939-954 (2015)
  3. Discovery and Characterization of ZUFSP/ZUP1, a Distinct Deubiquitinase Class Important for Genome Stability. Kwasna D, Abdul Rehman SA, Natarajan J, Matthews S, Madden R, De Cesare V, Weidlich S, Virdee S, Ahel I, Gibbs-Seymour I, Kulathu Y. Mol Cell 70 150-164.e6 (2018)
  4. Ubiquitin Linkage-Specific Affimers Reveal Insights into K6-Linked Ubiquitin Signaling. Michel MA, Swatek KN, Hospenthal MK, Komander D. Mol Cell 68 233-246.e5 (2017)
  5. Breast cancer metastasis suppressor OTUD1 deubiquitinates SMAD7. Zhang Z, Fan Y, Xie F, Zhou H, Jin K, Shao L, Shi W, Fang P, Yang B, van Dam H, Ten Dijke P, Zheng X, Yan X, Jia J, Zheng M, Jin J, Ding C, Ye S, Zhou F, Zhang L. Nat Commun 8 2116 (2017)
  6. Non-hydrolyzable Diubiquitin Probes Reveal Linkage-Specific Reactivity of Deubiquitylating Enzymes Mediated by S2 Pockets. Flierman D, van der Heden van Noort GJ, Ekkebus R, Geurink PP, Mevissen TE, Hospenthal MK, Komander D, Ovaa H. Cell Chem Biol 23 472-482 (2016)
  7. Linkage-specific conformational ensembles of non-canonical polyubiquitin chains. Castañeda CA, Chaturvedi A, Camara CM, Curtis JE, Krueger S, Fushman D. Phys Chem Chem Phys 18 5771-5788 (2016)
  8. Biochemical characterization of protease activity of Nsp3 from SARS-CoV-2 and its inhibition by nanobodies. Armstrong LA, Lange SM, Dee Cesare V, Matthews SP, Nirujogi RS, Cole I, Hope A, Cunningham F, Toth R, Mukherjee R, Bojkova D, Gruber F, Gray D, Wyatt PG, Cinatl J, Dikic I, Davies P, Kulathu Y. PLoS One 16 e0253364 (2021)
  9. Structural basis for specific cleavage of Lys6-linked polyubiquitin chains by USP30. Sato Y, Okatsu K, Saeki Y, Yamano K, Matsuda N, Kaiho A, Yamagata A, Goto-Ito S, Ishikawa M, Hashimoto Y, Tanaka K, Fukai S. Nat Struct Mol Biol 24 911-919 (2017)
  10. A single MIU motif of MINDY-1 recognizes K48-linked polyubiquitin chains. Kristariyanto YA, Abdul Rehman SA, Weidlich S, Knebel A, Kulathu Y. EMBO Rep 18 392-402 (2017)
  11. Mechanism of ubiquitin chain synthesis employed by a HECT domain ubiquitin ligase. French ME, Klosowiak JL, Aslanian A, Reed SI, Yates JR, Hunter T. J Biol Chem 292 10398-10413 (2017)
  12. A Rapid and Versatile Method for Generating Proteins with Defined Ubiquitin Chains. Martinez-Fonts K, Matouschek A. Biochemistry 55 1898-1908 (2016)
  13. 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)
  14. Structural insights into two distinct binding modules for Lys63-linked polyubiquitin chains in RNF168. Takahashi TS, Hirade Y, Toma A, Sato Y, Yamagata A, Goto-Ito S, Tomita A, Nakada S, Fukai S. Nat Commun 9 170 (2018)
  15. The deubiquitinase TRABID stabilizes the K29/K48-specific E3 ubiquitin ligase HECTD1. Harris LD, Le Pen J, Scholz N, Mieszczanek J, Vaughan N, Davis S, Berridge G, Kessler BM, Bienz M, Licchesi JDF. J Biol Chem 296 100246 (2021)
  16. Hepatitis B Core Protein Is Post-Translationally Modified through K29-Linked Ubiquitination. Langerová H, Lubyová B, Zábranský A, Hubálek M, Glendová K, Aillot L, Hodek J, Strunin D, Janovec V, Hirsch I, Weber J. Cells 9 E2547 (2020)
  17. KIAA0317 regulates pulmonary inflammation through SOCS2 degradation. Lear TB, McKelvey AC, Evankovich JW, Rajbhandari S, Coon TA, Dunn SR, Londino JD, McVerry BJ, Zhang Y, Valenzi E, Burton CL, Gordon R, Gingras S, Lockwood KC, Jurczak MJ, Lafyatis R, Shlomchik MJ, Liu Y, Chen BB. JCI Insight 4 129110 (2019)
  18. Mechanism of activation and regulation of deubiquitinase activity in MINDY1 and MINDY2. Abdul Rehman SA, Armstrong LA, Lange SM, Kristariyanto YA, Gräwert TW, Knebel A, Svergun DI, Kulathu Y. Mol Cell 81 4176-4190.e6 (2021)
  19. Structural insights into a HECT-type E3 ligase AREL1 and its ubiquitination activities in vitro. Singh S, Ng J, Nayak D, Sivaraman J. J Biol Chem 294 19934-19949 (2019)
  20. Synthesis of Branched Triubiquitin Active-Site Directed Probes. Liu J, Li Y, Deol KK, Strieter ER. Org Lett 21 6790-6794 (2019)
  21. Steady-state kinetic studies reveal that the anti-cancer target Ubiquitin-Specific Protease 17 (USP17) is a highly efficient deubiquitinating enzyme. Hjortland NM, Mesecar AD. Arch Biochem Biophys 612 35-45 (2016)
  22. The pros and cons of ubiquitination on the formation of protein condensates. Hou XN, Tang C. Acta Biochim Biophys Sin (Shanghai) 55 1084-1098 (2023)
  23. Diubiquitin-Based NMR Analysis: Interactions Between Lys6-Linked diUb and UBA Domain of UBXN1. Shahul Hameed D, van Tilburg GBA, Merkx R, Flierman D, Wienk H, El Oualid F, Hofmann K, Boelens R, Ovaa H. Front Chem 7 921 (2019)
  24. Hecw controls oogenesis and neuronal homeostasis by promoting the liquid state of ribonucleoprotein particles. Fajner V, Giavazzi F, Sala S, Oldani A, Martini E, Napoletano F, Parazzoli D, Cesare G, Cerbino R, Maspero E, Vaccari T, Polo S. Nat Commun 12 5488 (2021)
  25. TRABID overexpression enables synthetic lethality to PARP inhibitor via prolonging 53BP1 retention at double-strand breaks. Ma J, Zhou Y, Pan P, Yu H, Wang Z, Li LL, Wang B, Yan Y, Pan Y, Ye Q, Liu T, Feng X, Xu S, Wang K, Wang X, Jian Y, Ma B, Fan Y, Gao Y, Huang H, Li L. Nat Commun 14 1810 (2023)
  26. The E3 ubiquitin ligase HECTD1 contributes to cell proliferation through an effect on mitosis. Vaughan N, Scholz N, Lindon C, Licchesi JDF. Sci Rep 12 13160 (2022)
  27. The chemical biology of ubiquitin. Burslem GM. Biochim Biophys Acta Gen Subj 1866 130079 (2022)
  28. IL-1β turnover by the UBE2L3 ubiquitin conjugating enzyme and HECT E3 ligases limits inflammation. Mishra V, Crespo-Puig A, McCarthy C, Masonou T, Glegola-Madejska I, Dejoux A, Dow G, Eldridge MJG, Marinelli LH, Meng M, Wang S, Bennison DJ, Morrison R, Shenoy AR. Nat Commun 14 4385 (2023)