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Structural and biochemical studies of the open state of Lys48-linked diubiquitin.

Lai MY, Zhang D, Laronde-Leblanc N, Fushman D
Biochim Biophys Acta 1823 2046-56 (2012)
Cited: 30 times
EuropePMC logo PMID: 22542781

Abstract

Ubiquitin (Ub) is a small protein highly conserved among eukaryotes and involved in practically all aspects of eukaryotic cell biology. Polymeric chains assembled from covalently-linked Ub monomers function as molecular signals in the regulation of a host of cellular processes. Our previous studies have shown that the predominant state of Lys48-linked di- and tetra-Ub chains at near-physiological conditions is a closed conformation, in which the Ub-Ub interface is formed by the hydrophobic surface residues of the adjacent Ub units. Because these very residues are involved in (poly)Ub interactions with the majority of Ub-binding proteins, their sequestration at the Ub-Ub interface renders the closed conformation of polyUb binding incompetent. Thus the existence of open conformation(s) and the interdomain motions opening and closing the Ub-Ub interface is critical for the recognition of Lys48-linked polyUb by its receptors. Knowledge of the conformational properties of a polyUb signal is essential for our understanding of its specific recognition by various Ub-receptors. Despite their functional importance, open states of Lys48-linked chains are poorly characterized. Here we report a crystal structure of the open state of Lys48-linked di-Ub. Moreover, using NMR, we examined interactions of the open state of this chain (at pH4.5) with a Lys48-linkage-selective receptor, the UBA2 domain of a shuttle protein hHR23a. Our results show that di-Ub binds UBA2 in the same mode and with comparable affinity as the closed state. Our data suggest a mechanism for polyUb signal recognition, whereby Ub-binding proteins select specific conformations out of the available ensemble of polyUb chain conformations. This article is part of a Special Issue entitled: Ubiquitin Drug Discovery and Diagnostics.

Articles - 3ns8 mentioned but not cited (13)

  1. Recovering a representative conformational ensemble from underdetermined macromolecular structural data. Berlin K, Castañeda CA, Schneidman-Duhovny D, Sali A, Nava-Tudela A, Fushman D. J Am Chem Soc 135 16595-16609 (2013)
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  3. Structural and biochemical studies of the open state of Lys48-linked diubiquitin. Lai MY, Zhang D, Laronde-Leblanc N, Fushman D. Biochim Biophys Acta 1823 2046-2056 (2012)
  4. Feedback inhibition of cAMP effector signaling by a chaperone-assisted ubiquitin system. Rinaldi L, Delle Donne R, Catalanotti B, Torres-Quesada O, Enzler F, Moraca F, Nisticò R, Chiuso F, Piccinin S, Bachmann V, Lindner HH, Garbi C, Scorziello A, Russo NA, Synofzik M, Stelzl U, Annunziato L, Stefan E, Feliciello A. Nat Commun 10 2572 (2019)
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  12. research-article Dual domain recognition determines SARS-CoV-2 PLpro selectivity for human ISG15 and K48-linked di-ubiquitin. Wydorski PM, Osipiuk J, Lanham BT, Tesar C, Endres M, Engle E, Jedrzejczak R, Mullapudi V, Michalska K, Fidelis K, Fushman D, Joachimiak A, Joachimiak LA. bioRxiv 2021.09.15.460543 (2023)
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Reviews citing this publication (1)

  1. Proteasome interaction with ubiquitinated substrates: from mechanisms to therapies. Chen X, Htet ZM, López-Alfonzo E, Martin A, Walters KJ. FEBS J 288 5231-5251 (2021)

Articles citing this publication (16)

  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)
  2. Recognition and cleavage of related to ubiquitin 1 (Rub1) and Rub1-ubiquitin chains by components of the ubiquitin-proteasome system. Singh RK, Zerath S, Kleifeld O, Scheffner M, Glickman MH, Fushman D. Mol Cell Proteomics 11 1595-1611 (2012)
  3. The Colossus of ubiquitylation: decrypting a cellular code. Williamson A, Werner A, Rape M. Mol Cell 49 591-600 (2013)
  4. Ubiquitin S65 phosphorylation engenders a pH-sensitive conformational switch. Dong X, Gong Z, Lu YB, Liu K, Qin LY, Ran ML, Zhang CL, Liu Z, Zhang WP, Tang C. Proc Natl Acad Sci U S A 114 6770-6775 (2017)
  5. An Extended Conformation for K48 Ubiquitin Chains Revealed by the hRpn2:Rpn13:K48-Diubiquitin Structure. Lu X, Ebelle DL, Matsuo H, Walters KJ. Structure 28 495-506.e3 (2020)
  6. Towards a molecular basis of ubiquitin signaling: A dual-scale simulation study of ubiquitin dimers. Berg A, Kukharenko O, Scheffner M, Peter C. PLoS Comput Biol 14 e1006589 (2018)
  7. 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)
  8. The Vps27/Hrs/STAM (VHS) Domain of the Signal-transducing Adaptor Molecule (STAM) Directs Associated Molecule with the SH3 Domain of STAM (AMSH) Specificity to Longer Ubiquitin Chains and Dictates the Position of Cleavage. Baiady N, Padala P, Mashahreh B, Cohen-Kfir E, Todd EA, Du Pont KE, Berndsen CE, Wiener R. J Biol Chem 291 2033-2042 (2016)
  9. Unexpected trypsin cleavage at ubiquitinated lysines. Burke MC, Wang Y, Lee AE, Dixon EK, Castaneda CA, Fushman D, Fenselau C. Anal Chem 87 8144-8148 (2015)
  10. Solution structure of lysine-free (K0) ubiquitin. Huang T, Li J, Byrd RA. Protein Sci 23 662-667 (2014)
  11. A snapshot of ubiquitin chain elongation: lysine 48-tetra-ubiquitin slows down ubiquitination. Kovacev J, Wu K, Spratt DE, Chong RA, Lee C, Nayak J, Shaw GS, Pan ZQ. J Biol Chem 289 7068-7081 (2014)
  12. New conformations of linear polyubiquitin chains from crystallographic and solution-scattering studies expand the conformational space of polyubiquitin. Thach TT, Shin D, Han S, Lee S. Acta Crystallogr D Struct Biol 72 524-535 (2016)
  13. Activated Protein C Ameliorates Diabetic Cardiomyopathy via Modulating OTUB1/YB-1/MEF2B Axis. Zhong X, Wang T, Xie Y, Wang M, Zhang W, Dai L, Lai J, Nie X, He X, Madhusudhan T, Zeng H, Wang H. Front Cardiovasc Med 8 758158 (2021)
  14. An integrated approach of NMR experiments and MD simulations visualizes structural dynamics of a cyclic multi-domain protein. Sorada T, Walinda E, Shirakawa M, Sugase K, Morimoto D. Protein Sci 32 e4768 (2023)
  15. 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)
  16. Mutational and Environmental Effects on the Dynamic Conformational Distributions of Lys48-Linked Ubiquitin Chains. Hiranyakorn M, Yagi-Utsumi M, Yanaka S, Ohtsuka N, Momiyama N, Satoh T, Kato K. Int J Mol Sci 24 6075 (2023)


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