Structural basis for the RING-catalyzed synthesis of K63-linked ubiquitin chains
MetadataShow full item record
The RING E3 ligase catalysed formation of lysine 63 linked ubiquitin chains by the Ube2V2–Ubc13 E2 complex is required for many important biological processes. Here we report the structure of the RING domain dimer of rat RNF4 in complex with a human Ubc13~Ub conjugate and Ube2V2. The structure has captured Ube2V2 bound to the acceptor (priming) ubiquitin with Lys63 in a position that could lead to attack on the linkage between the donor (second) ubiquitin and Ubc13 that is held in the active “folded back” conformation by the RING domain of RNF4. The interfaces identified in the structure were verified by in vitro ubiquitination assays of site directed mutants. This represents the first view of the synthesis of Lys63 linked ubiquitin chains in which both substrate ubiquitin and ubiquitin-loaded E2 are juxtaposed to allow E3 ligase mediated catalysis.
Branigan , E , Plechanovová , A , Jaffray , E , Naismith , J & Hay , R T 2015 , ' Structural basis for the RING-catalyzed synthesis of K63-linked ubiquitin chains ' , Nature Structural and Molecular Biology , vol. 22 , no. 8 , pp. 597-602 . https://doi.org/10.1038/nsmb.3052
Nature Structural and Molecular Biology
Copyright 2015 the Authors. This work is made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://dx.doi.org/10.1038/nsmb.3052. Users may view, print, copy, download and text and data-mine this content, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/policies/license.html.
DescriptionThis work was supported by grants from Cancer Research UK (C434/A13067), the Wellcome Trust (098391/Z/12/Z) and Biotechnology and Biological Sciences Research Council (BB/J016004/1).
Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.