2jgz

From Proteopedia

Revision as of 12:43, 23 January 2008

CRYSTAL STRUCTURE OF PHOSPHO-CDK2 IN COMPLEX WITH CYCLIN B

Overview

The transitions of the cell cycle are regulated by the cyclin dependent, protein kinases (CDKs). The cyclins activate their respective CDKs and, confer substrate recognition properties. We report the structure of, phospho-CDK2/cyclin B and show that cyclin B confers M phase-like, properties on CDK2, the kinase that is usually associated with S phase., Cyclin B produces an almost identical activated conformation of CDK2 as, that produced by cyclin A. There are differences between cyclin A and, cyclin B at the recruitment site, which in cyclin A is used to recruit, substrates containing an RXL motif. Because of sequence differences this, site in cyclin B binds RXL motifs more weakly than in cyclin A. Despite, similarity in kinase structures, phospho-CDK2/cyclin B phosphorylates, substrates, such as nuclear lamin and a model peptide derived from p107, at sequences SPXX that differ from the canonical CDK2/cyclin A substrate, recognition motif, SPXK. CDK2/cyclin B phosphorylation at these, non-canonical sites is not dependent on the presence of a RXL recruitment, motif. The p107 peptide contains two SP motifs each followed by a, non-canonical sequence of which only one site (Ser640) is phosphorylated, by pCDK2/cyclin A while two sites are phosphorylated by pCDK2/cyclin B., The second site is too close to the RXL motif to allow the cyclin A, recruitment site to be effective, as previous work has shown that there, must be at least 16 residues between the catalytic site serine and the RXL, motif. Thus the cyclins A and B in addition to their role in promoting the, activatory conformational switch in CDK2, also provide differential, substrate specificity.

About this Structure

2JGZ is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Cyclin B and cyclin A confer different substrate recognition properties on CDK2., Brown NR, Lowe ED, Petri E, Skamnaki V, Antrobus R, Johnson LN, Cell Cycle. 2007 Jun;6(11):1350-9. Epub 2007 Jun 11. PMID:17495531

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