Crystal structure and mutational analysis of the human CDK2 kinase complex with cell cycle-regulatory protein CksHs1

Cell. 1996 Mar 22;84(6):863-74. doi: 10.1016/s0092-8674(00)81065-x.

Abstract

The 2.6 Angstrom crystal structure for human cyclin-dependent kinase 2(CDK2) in complex with CksHs1, a human homolog of essential yeast cell cycle-regulatory proteins suc1 and Cks1, reveals that CksHs1 binds via all four beta strands to the kinase C-terminal lobe. This interface is biologically critical, based upon mutational analysis, but far from the CDK2 N-terminal lobe, cyclin, and regulatory phosphorylation sites. CDK2 binds the Cks single domain conformation and interacts with conserved hydrophobic residues plus His-60 and Glu-63 in their closed beta-hinge motif conformation. The beta hinge opening to form the Cks beta-interchanged dimer sterically precludes CDK2 binding, providing a possible mechanism regulating CDK2-Cks interactions. One face of the complex 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • CDC2-CDC28 Kinases*
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Cycle / physiology
  • Cell Cycle Proteins*
  • Conserved Sequence
  • Crystallography
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases / chemistry*
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism
  • DNA Mutational Analysis
  • Humans
  • Image Processing, Computer-Assisted
  • Molecular Sequence Data
  • Protein Binding / physiology
  • Protein Conformation
  • Protein Kinases*
  • Protein-Serine-Threonine Kinases / chemistry*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Saccharomyces cerevisiae / genetics
  • Sensitivity and Specificity
  • Sequence Homology, Amino Acid

Substances

  • CKS1B protein, human
  • Carrier Proteins
  • Cell Cycle Proteins
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • CKS2 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases