Phosphoprotein-protein interactions revealed by the crystal structure of kinase-associated phosphatase in complex with PhosphoCDK2

Citation
Hw. Song et al., Phosphoprotein-protein interactions revealed by the crystal structure of kinase-associated phosphatase in complex with PhosphoCDK2, MOL CELL, 7(3), 2001, pp. 615-626
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
MOLECULAR CELL
ISSN journal
1097-2765 → ACNP
Volume
7
Issue
3
Year of publication
2001
Pages
615 - 626
Database
ISI
SICI code
1097-2765(200103)7:3<615:PIRBTC>2.0.ZU;2-7
Abstract
The CDK-interacting protein phosphatase KAP dephosphorylates phosphoThr-160 (pThr-160) of the CDK2 activation segment, the site of regulatory phosphor ylation that is essential for kinase activity. Here we describe the crystal structure of KAP in association with pThr-160-CDK2, representing an exampl e of a protein phosphatase in complex with its intact protein substrate. Th e major protein interface between the two molecules is formed by the C-term inal lobe of CDK2 and the C-terminal helix of KAP, regions remote from the kinase-activation segment and the KAP catalytic site. The kinase-activation segment interacts with the catalytic site of KAP almost entirely via the p hosphate group of pThr-160. This interaction requires that the activation s egment is unfolded and drawn away from the kinase molecule, inducing a conf ormation of CDK2 similar to the activated state observed in the CDK2/cyclin A complex.