Y. Bourne et al., CRYSTAL-STRUCTURE AND MUTATIONAL ANALYSIS THE HUMAN CDK2 KINASE COMPLEX WITH CELL CYCLE-REGULATORY PROTEIN CKSHS1, Cell, 84(6), 1996, pp. 863-874
The 2.6 Angstrom crystal structure for human cyclin-dependent kinase 2
(CDK2) in complex with CksHs1, a human homolog of essential yeast cel
l cycle-regulatory proteins suc1 and Cks1, reveals that CksHs1 binds v
ia all four beta strands to the kinase C-terminal robe. This interface
is biologically critical, based upon mutational analysis, but far fro
m the CDK2 N-terminal lobe, cyclin, and regulatory phosphorylation sit
es. CDK2 binds the Cks single domain conformation and interacts with c
onserved hydrophobic residues plus His-60 and Glu-63 in their closed b
eta-hinge motif conformation. The beta hinge opening to form the Cks b
eta-interchanged dimer sterically precludes CDK2 binding, providing a
possible mechanism regulating CDK2-Cks interactions. One face of the c
omplex exposes the sequence-conserved phosphate-binding region on Cks
and the ATP-binding site on CDK2, suggesting that Cks may target CDK2
to other phosphoproteins during the cell cycle.