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A human ubiquitin conjugating enzyme (E2)-HECT E3 ligase structure-function screen.

Sheng Y, Hong JH, Doherty R, Srikumar T, Shloush J, Avvakumov GV, Walker JR, Xue S, Neculai D, Wan JW, Kim SK, Arrowsmith CH, Raught B, Dhe-Paganon S
Mol Cell Proteomics 11 329-41 (2012)
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Cited: 79 times
EuropePMC logo PMID: 22496338

Abstract

Here we describe a systematic structure-function analysis of the human ubiquitin (Ub) E2 conjugating proteins, consisting of the determination of 15 new high-resolution three-dimensional structures of E2 catalytic domains, and autoubiquitylation assays for 26 Ub-loading E2s screened against a panel of nine different HECT (homologous to E6-AP carboxyl terminus) E3 ligase domains. Integration of our structural and biochemical data revealed several E2 surface properties associated with Ub chain building activity; (1) net positive or neutral E2 charge, (2) an "acidic trough" located near the catalytic Cys, surrounded by an extensive basic region, and (3) similarity to the previously described HECT binding signature in UBE2L3 (UbcH7). Mass spectrometry was used to characterize the autoubiquitylation products of a number of functional E2-HECT pairs, and demonstrated that HECT domains from different subfamilies catalyze the formation of very different types of Ub chains, largely independent of the E2 in the reaction. Our data set represents the first comprehensive analysis of E2-HECT E3 interactions, and thus provides a framework for better understanding the molecular mechanisms of ubiquitylation.

Reviews - 2f4w mentioned but not cited (1)

  1. Structural basis of generic versus specific E2-RING E3 interactions in protein ubiquitination. Gundogdu M, Walden H. Protein Sci 28 1758-1770 (2019)

Articles - 2f4w mentioned but not cited (8)

  1. A human ubiquitin conjugating enzyme (E2)-HECT E3 ligase structure-function screen. Sheng Y, Hong JH, Doherty R, Srikumar T, Shloush J, Avvakumov GV, Walker JR, Xue S, Neculai D, Wan JW, Kim SK, Arrowsmith CH, Raught B, Dhe-Paganon S. Mol Cell Proteomics 11 329-341 (2012)
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Reviews citing this publication (11)

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  5. Targeting HECT-type E3 ligases - insights from catalysis, regulation and inhibitors. Fajner V, Maspero E, Polo S. FEBS Lett 591 2636-2647 (2017)
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Articles citing this publication (59)

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  34. Mind the Metal: A Fragment Library-Derived Zinc Impurity Binds the E2 Ubiquitin-Conjugating Enzyme Ube2T and Induces Structural Rearrangements. Morreale FE, Testa A, Chaugule VK, Bortoluzzi A, Ciulli A, Walden H. J Med Chem 60 8183-8191 (2017)
  35. Evaluation of Reference Genes for Quantitative Real-Time PCR Analysis of the Gene Expression in Laticifers on the Basis of Latex Flow in Rubber Tree (Hevea brasiliensis Muell. Arg.). Chao J, Yang S, Chen Y, Tian WM. Front Plant Sci 7 1149 (2016)
  36. Hepatitis C Virus Downregulates Ubiquitin-Conjugating Enzyme E2S Expression To Prevent Proteasomal Degradation of NS5A, Leading to Host Cells More Sensitive to DNA Damage. Pham HT, Nguyen TTT, Nguyen LP, Han SS, Lim YS, Hwang SB. J Virol 93 e01240-18 (2019)
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  41. Dimerization regulates the human APC/C-associated ubiquitin-conjugating enzyme UBE2S. Liess AKL, Kucerova A, Schweimer K, Schlesinger D, Dybkov O, Urlaub H, Mansfeld J, Lorenz S. Sci Signal 13 eaba8208 (2020)
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