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
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.