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Crystal structure of cyclic Lys48-linked tetraubiquitin.

Satoh T, Sakata E, Yamamoto S, Yamaguchi Y, Sumiyoshi A, Wakatsuki S, Kato K
Biochem Biophys Res Commun 400 329-33 (2010)
Cited: 16 times
EuropePMC logo PMID: 20728431

Abstract

Lys48-linked polyubiquitin chains serve as a signal for protein degradation by 26S proteasomes through its Ile44 hydrophobic patches interactions. The individual ubiquitin units of each chain are conjugated through an isopeptide bond between Lys48 and the C-terminal Gly76 of the preceding units. The conformation of Lys48-linked tetraubiquitin has been shown to change dynamically depending on solution pH. Here we enzymatically synthesized a wild-type Lys48-linked tetraubiquitin for structural study. In the synthesis, cyclic and non-cyclic species were obtained as major and minor fractions, respectively. This enabled us to solve the crystal structure of tetraubiquitin exclusively with native Lys48-linkages at 1.85A resolution in low pH 4.6. The crystallographic data clearly showed that the C-terminus of the first ubiquitin is conjugated to the Lys48 residue of the fourth ubiquitin. The overall structure is quite similar to the closed form of engineered tetraubiquitin at near-neutral pH 6.7, previously reported, in which the Ile44 hydrophobic patches face each other. The structure of the second and the third ubiquitin units [Ub(2)-Ub(3)] connected through a native isopeptide bond is significantly different from the conformations of the corresponding linkage of the engineered tetraubiquitins, whereas the structures of Ub(1)-Ub(2) and Ub(3)-Ub(4) isopeptide bonds are almost identical to those of the previously reported structures. From these observations, we suggest that the flexible nature of the isopeptide linkage thus observed contributes to the structural arrangements of ubiquitin chains exemplified by the pH-dependent closed-to-open conformational transition of tetraubiquitin.

Articles - 3alb mentioned but not cited (6)

  1. 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)
  2. 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)
  3. Determining Atomistic SAXS Models of Tri-Ubiquitin Chains from Bayesian Analysis of Accelerated Molecular Dynamics Simulations. Bowerman S, Rana ASJB, Rice A, Pham GH, Strieter ER, Wereszczynski J. J Chem Theory Comput 13 2418-2429 (2017)
  4. NMR Characterization of Conformational Interconversions of Lys48-Linked Ubiquitin Chains. Hiranyakorn M, Yanaka S, Satoh T, Wilasri T, Jityuti B, Yagi-Utsumi M, Kato K. Int J Mol Sci 21 E5351 (2020)
  5. CARDIO-PRED: an in silico tool for predicting cardiovascular-disorder associated proteins. Jain P, Thukral N, Gahlot LK, Hasija Y. Syst Synth Biol 9 55-66 (2015)
  6. Enhancing ubiquitin crystallization through surface-entropy reduction. Loll PJ, Xu P, Schmidt JT, Melideo SL. Acta Crystallogr F Struct Biol Commun 70 1434-1442 (2014)


Reviews citing this publication (3)

  1. Proteasome in action: substrate degradation by the 26S proteasome. Sahu I, Glickman MH. Biochem Soc Trans 49 629-644 (2021)
  2. [Structural biology of post-translational modifications of proteins]. Kato K. Yakugaku Zasshi 132 563-573 (2012)
  3. Exploiting E3 ubiquitin ligases to reeducate the tumor microenvironment for cancer therapy. Li XM, Zhao ZY, Yu X, Xia QD, Zhou P, Wang SG, Wu HL, Hu J. Exp Hematol Oncol 12 34 (2023)

Articles citing this publication (7)

  1. In Vivo Ubiquitin Linkage-type Analysis Reveals that the Cdc48-Rad23/Dsk2 Axis Contributes to K48-Linked Chain Specificity of the Proteasome. Tsuchiya H, Ohtake F, Arai N, Kaiho A, Yasuda S, Tanaka K, Saeki Y. Mol Cell 66 488-502.e7 (2017)
  2. Conformational dynamics of wild-type Lys-48-linked diubiquitin in solution. Hirano T, Serve O, Yagi-Utsumi M, Takemoto E, Hiromoto T, Satoh T, Mizushima T, Kato K. J Biol Chem 286 37496-37502 (2011)
  3. Loop 7 of E2 enzymes: an ancestral conserved functional motif involved in the E2-mediated steps of the ubiquitination cascade. Papaleo E, Casiraghi N, Arrigoni A, Vanoni M, Coccetti P, De Gioia L. PLoS One 7 e40786 (2012)
  4. NMR characterization of the interaction between the PUB domain of peptide:N-glycanase and ubiquitin-like domain of HR23. Kamiya Y, Uekusa Y, Sumiyoshi A, Sasakawa H, Hirao T, Suzuki T, Kato K. FEBS Lett 586 1141-1146 (2012)
  5. Structural basis for the recognition of K48-linked Ub chain by proteasomal receptor Rpn13. Liu Z, Dong X, Yi HW, Yang J, Gong Z, Wang Y, Liu K, Zhang WP, Tang C. Cell Discov 5 19 (2019)
  6. Structural insights into pro-aggregation effects of C. elegans CRAM-1 and its human ortholog SERF2. Balasubramaniam M, Ayyadevara S, Shmookler Reis RJ. Sci Rep 8 14891 (2018)
  7. Cyclisation of Lys48-linked diubiquitin in vitro and in vivo. Sokratous K, Strachan J, Roach LV, Layfield R, Oldham NJ. FEBS Lett 586 4144-4147 (2012)


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