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2ast

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2ast, resolution 2.30Å ()
Ligands:
Non-Standard Residues:
Gene: SKP1A, EMC19, OCP2, SKP1, TCEB1L (Homo sapiens), SKP2, FBXL1 (Homo sapiens), CKS1, CKS1B (Homo sapiens)
Domains: Skp1, Skp1, SKP1, CKS, FBOX
Related: 2ass, 1fqv
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Crystal structure of Skp1-Skp2-Cks1 in complex with a p27 peptide

Publication Abstract from PubMed

The ubiquitin-mediated proteolysis of the Cdk2 inhibitor p27(Kip1) plays a central role in cell cycle progression, and enhanced degradation of p27(Kip1) is associated with many common cancers. Proteolysis of p27(Kip1) is triggered by Thr187 phosphorylation, which leads to the binding of the SCF(Skp2) (Skp1-Cul1-Rbx1-Skp2) ubiquitin ligase complex. Unlike other known SCF substrates, p27(Kip1) ubiquitination also requires the accessory protein Cks1. The crystal structure of the Skp1-Skp2-Cks1 complex bound to a p27(Kip1) phosphopeptide shows that Cks1 binds to the leucine-rich repeat (LRR) domain and C-terminal tail of Skp2, whereas p27(Kip1) binds to both Cks1 and Skp2. The phosphorylated Thr187 side chain of p27(Kip1) is recognized by a Cks1 phosphate binding site, whereas the side chain of an invariant Glu185 inserts into the interface between Skp2 and Cks1, interacting with both. The structure and biochemical data support the proposed model that Cdk2-cyclin A contributes to the recruitment of p27(Kip1) to the SCF(Skp2)-Cks1 complex.

Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase., Hao B, Zheng N, Schulman BA, Wu G, Miller JJ, Pagano M, Pavletich NP, Mol Cell. 2005 Oct 7;20(1):9-19. PMID:16209941

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

2AST is a 4 chains structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  • Hao B, Zheng N, Schulman BA, Wu G, Miller JJ, Pagano M, Pavletich NP. Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase. Mol Cell. 2005 Oct 7;20(1):9-19. PMID:16209941 doi:10.1016/j.molcel.2005.09.003

Page seeded by OCA on Mon Feb 16 21:03:01 2009

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