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The structural basis for specificity of substrate and recruitment peptides for cyclin-dependent kinases

The structural basis for specificity of substrate and recruitment peptides for cyclin-dependent... Progression through the eukaryotic cell cycle is driven by the orderly activation of cyclin-dependent kinases (CDKs). For activity, CDKs require association with a cyclin and phosphorylation by a separate protein kinase at a conserved threonine residue (T160 in CDK2). Here we present the structure of a complex consisting of phosphorylated CDK2 and cyclin A together with an optimal peptide substrate, HHASPRK. This structure provides an explanation for the specificity of CDK2 towards the proline that follows the phosphorylatable serine of the substrate peptide, and the requirement for the basic residue in the P+3 position of the substrate. We also present the structure of phosphorylated CDK2 plus cyclin A3 in complex with residues 658–668 from the CDK2 substrate p107. These residues include the RXL motif required to target p107 to cyclins. This structure explains the specificity of the RXL motif for cyclins. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Cell Biology Springer Journals

The structural basis for specificity of substrate and recruitment peptides for cyclin-dependent kinases

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References (38)

Publisher
Springer Journals
Copyright
Copyright © 1999 by Macmillan Magazines Ltd.
Subject
Life Sciences; Life Sciences, general; Cell Biology; Cancer Research; Developmental Biology; Stem Cells
ISSN
1465-7392
eISSN
1476-4679
DOI
10.1038/15674
Publisher site
See Article on Publisher Site

Abstract

Progression through the eukaryotic cell cycle is driven by the orderly activation of cyclin-dependent kinases (CDKs). For activity, CDKs require association with a cyclin and phosphorylation by a separate protein kinase at a conserved threonine residue (T160 in CDK2). Here we present the structure of a complex consisting of phosphorylated CDK2 and cyclin A together with an optimal peptide substrate, HHASPRK. This structure provides an explanation for the specificity of CDK2 towards the proline that follows the phosphorylatable serine of the substrate peptide, and the requirement for the basic residue in the P+3 position of the substrate. We also present the structure of phosphorylated CDK2 plus cyclin A3 in complex with residues 658–668 from the CDK2 substrate p107. These residues include the RXL motif required to target p107 to cyclins. This structure explains the specificity of the RXL motif for cyclins.

Journal

Nature Cell BiologySpringer Journals

Published: Oct 14, 1999

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