4HS2

Crystal Structure of the Human SPOP C-terminal Domain

Summary for 4HS2

• Entry DOI: 10.2210/pdb4hs2/pdb
• Descriptor: Speckle-type POZ protein (2 entities in total)
• Functional Keywords: protein interaction domain, oligomerisation, protein binding
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: O43791
• Total number of polymer chains: 1
• Total formula weight: 11941.45

Authors

Van Geersdaele, L.K.,Stead, M.A.,Carr, S.B.,Wright, S.C. (deposition date: 2012-10-29, release date: 2013-09-11, Last modification date: 2024-02-28)

Primary citation

van Geersdaele, L.K.,Stead, M.A.,Harrison, C.M.,Carr, S.B.,Close, H.J.,Rosbrook, G.O.,Connell, S.D.,Wright, S.C.
Structural basis of high-order oligomerization of the cullin-3 adaptor SPOP.
Acta Crystallogr.,Sect.D, 69:1677-1684, 2013

PubMed 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.

PubMed: 23999291
DOI: 10.1107/S0907444913012687

Experimental method

X-RAY DIFFRACTION (1.53 Å)