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Structural basis of high-order oligomerization of the cullin-3 adaptor SPOP

DOI: 10.1107/S0907444913012687 DOI Help
PMID: 23999291 PMID Help

Authors: Laura Van Geersdaele (University of Leeds) , Mark Stead (School of Biology, University of Leeds) , Christopher Harrison (University of Leeds) , Stephen Carr (Membrane Protein Laboratory, Diamond Light Source) , Helen Close (University of Leeds) , Gareth Rosbrook (Institute of Molecular and Cellular Biology, University of Leeds) , Simon D. Connell (University of Leeds) , Stephanie Wright (University of Leeds)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acta Crystallographica Section D Biological Crystallography , VOL 69 , PAGES 1677 - 1684

State: Published (Approved)
Published: September 2013

Abstract: Protein ubiquitination in eukaryotic cells is mediated by diverse E3 ligase enzymes that each target specific substrates. The cullin E3 ligase complexes are the most abundant class of E3 ligases; they contain various cullin components that serve as scaffolds for interaction with substrate-recruiting adaptor proteins. SPOP is a BTB-domain adaptor of the cullin-3 E3 ligase complexes; it selectively recruits substrates via its N-­terminal MATH domain, whereas its BTB domain mediates dimerization and interactions with cullin-3. It has recently been recognized that the high-order oligomerization of SPOP enhances the ubiquitination of substrates. Here, a dimerization interface in the SPOP C-terminus is identified and it is shown that the dimerization interfaces of the BTB domain and of the C-terminus act independently and in tandem to generate high-order SPOP oligomers. The crystal structure of the dimeric SPOP C-terminal domain is reported at 1.5 Å resolution and it is shown that Tyr353 plays a critical role in high-order oligomerization. A model of the high-order SPOP oligomer is presented that depicts a helical organization that could enhance the efficiency of substrate ubiquitination.

Journal Keywords: Crystallography; X-Ray; Cullin; Humans; Microscopy; Atomic; Models; Chemical; Nuclear; Protein; Secondary; Protein; Tertiary; Repressor; Substrate; Ubiquitin-Protein; Ubiquitination; Up-Regulation

Subject Areas: Biology and Bio-materials

Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength)

Added On: 28/08/2013 11:22

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