Adaptor Protein Self-Assembly Drives the Control of a Cullin-RING Ubiquitin Ligase

被引：124

作者：

Errington, Wesley J. ^{[1
]}

Khan, M. Qasim ^{[1
]}

Bueler, Stephanie A. ^{[2
]}

Rubinstein, John L. ^{[1
,2
,3
]}

Chakrabartty, Avijit ^{[1
,3
,4
]}

Prive, Gilbert G. ^{[1
,3
,4
]}

机构：

[1] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada

[2] Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada

[3] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada

[4] Ontario Canc Inst, Campbell Family Inst Canc Res, Toronto, ON M5G 1L7, Canada

来源：

STRUCTURE | 2012年 / 20卷 / 07期

关键词：

BTB DOMAIN; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; HISTONE DEACETYLASE; SUBSTRATE ADAPTERS; COMPLEX; DIMERIZATION; ACTIVATION; IDENTIFICATION; RECOGNITION;

D O I：

10.1016/j.str.2012.04.009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 angstrom 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.

引用

页码：1141 / 1153

页数：13

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