Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligase Complex

Cardote, Teresa A F and Gadd, Morgan S and Ciulli, Alessio (2017) Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligase Complex. Structure, 25 (6). 901-911.e3. ISSN 0969-2126

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Abstract

Cullin RING E3 ubiquitin ligases (CRLs) function in the ubiquitin proteasome system to catalyze the transfer of ubiquitin from E2 conjugating enzymes to specific substrate proteins. CRLs are large dynamic complexes and attractive drug targets for the development of small-molecule inhibitors and chemical inducers of protein degradation. The atomic details of whole CRL assembly and interactions that dictate subunit specificity remain elusive. Here we present the crystal structure of a pentameric CRL2VHL complex, composed of Cul2, Rbx1, Elongin B, Elongin C, and pVHL. The structure traps a closed state of full-length Cul2 and a new pose of Rbx1 in a trajectory from closed to open conformation. We characterize hotspots and binding thermodynamics at the interface between Cul2 and pVHL-EloBC and identify mutations that contribute toward a selectivity switch for Cul2 versus Cul5 recognition. Our findings provide structural and biophysical insights into the whole Cul2 complex that could aid future drug targeting.

Item Type: Journal Article
Journal or Publication Title: Structure
Additional Information: Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Subjects:
Departments: Faculty of Health and Medicine > Biomedical & Life Sciences
ID Code: 89194
Deposited By: ep_importer_pure
Deposited On: 14 Dec 2017 09:48
Refereed?: Yes
Published?: Published
Last Modified: 19 Feb 2020 04:14
URI: https://eprints.lancs.ac.uk/id/eprint/89194

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