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Sequential poly-ubiquitylation by specialized conjugating enzymes expands the versatility of a quality control ubiquitin ligase

Official URL:https://doi.org/10.1016/j.molcel.2016.07.020
PubMed:View item in PubMed
Creators Name:Weber, A. and Cohen, I. and Popp, O. and Dittmar, G. and Reiss, Y. and Sommer, T. and Ravid, T. and Jarosch, E.
Journal Title:Molecular Cell
Journal Abbreviation:Mol Cell
Volume:63
Number:5
Page Range:827-839
Date:1 September 2016
Abstract:The Doa10 quality control ubiquitin (Ub) ligase labels proteins with uniform lysine 48-linked poly-Ub (K48-pUB) chains for proteasomal degradation. Processing of Doa10 substrates requires the activity of two Ub conjugating enzymes. Here we show that the non-canonical conjugating enzyme Ubc6 attaches single Ub molecules not only to lysines but also to hydroxylated amino acids. These Ub moieties serve as primers for subsequent poly-ubiquitylation by Ubc7. We propose that the evolutionary conserved propensity of Ubc6 to mount Ub on diverse amino acids augments the number of ubiquitylation sites within a substrate and thereby increases the target range of Doa10. Our work provides new insights on how the consecutive activity of two specialized conjugating enzymes facilitates the attachment of poly-Ub to very heterogeneous client molecules. Such stepwise ubiquitylation reactions most likely represent a more general cellular phenomenon that extends the versatility yet sustains the specificity of the Ub conjugation system.
ISSN:1097-2765
Publisher:Cell Press / Elsevier (U.S.A.)
Item Type:Article

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