Adaptor protein self-assembly drives the control of a cullin-RING ubiquitin ligase

Wesley J. Errington, M. Qasim Khan, Stephanie A. Bueler, John L. Rubinstein, Avijit Chakrabartty, Gilbert G. Privé

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

The E3 ligases recruit substrate proteins for targeted ubiquitylation. Recent insights into the mechanisms of ubiquitylation demonstrate that E3 ligases can possess active regulatory properties beyond those of a simple assembly scaffold. Here, we describe the dimeric structure of the E3 ligase adaptor protein SPOP (speckle-type POZ protein) in complex with the N-terminal domain of Cul3 at 2.4 Å resolution. We find that SPOP forms large oligomers that can form heteromeric species with the closely related paralog SPOPL. In combination, SPOP and SPOPL (SPOP-like) form a molecular rheostat that can fine-tune E3 ubiquitin ligase activity by affecting the oligomeric state of the E3 complex. We propose that adaptor protein self-assembly provides a graded level of regulation of the SPOP/Cul3 E3 ligase toward its multiple protein substrates.

Original languageEnglish (US)
Pages (from-to)1141-1153
Number of pages13
JournalStructure
Volume20
Issue number7
DOIs
StatePublished - Jul 3 2012

Bibliographical note

Funding Information:
We thank Frank Sicheri, Steve Orlicky, Yang-Chieh Chou, and Cheryl Arrowsmith for baculovirus expression reagents. Lu Chen and Doug Kuntz established the baculovirus expression methods. We thank the Advanced Photon Source at the Argonne National Laboratory for access to the SBC-CAT 19 ID synchrotron facilities. Argonne is operated by UChicago Argonne, LLC, for the U.S. Department of Energy, Office of Biological and Environmental Research under contract DE-AC02-06CH11357. This research was funded in part by the Ontario Ministry of Health and Long Term Care. The views expressed do not necessarily reflect those of the OMOHLTC. W.J.E. was supported by a fellowship from the Canadian Cancer Society. G.G.P. was funded by grants from the CCSRI and the Samuel Waxman Cancer Research Foundation.

Fingerprint

Dive into the research topics of 'Adaptor protein self-assembly drives the control of a cullin-RING ubiquitin ligase'. Together they form a unique fingerprint.

Cite this