HUMAN CKSHS2 ATOMIC-STRUCTURE - A ROLE FOR ITS HEXAMERIC ASSEMBLY IN CELL-CYCLE CONTROL

The cell cycle regulatory protein CksHs2 binds to the catalytic subuni t of the cyclin-dependent kinases (Cdk's) and is essential for their b iological function. The crystal structure of the protein was determine d at 2.1 angstrom resolution. The CksHs2 structure is an unexpected he xamer formed by the symmetric assembly of three interlocked dimers int o an unusual 12-stranded beta barrel fold that may represent a prototy pe for this class of protein structures. Sequence-conserved regions fo rm the unusual beta strand exchange between the subunits of the dimer, and the metal and anion binding sites associated with the hexamer ass embly. The two other sequence-conserved regions line a 12 angstrom dia meter tunnel through the beta barrel and form the six exposed, charged helix pairs. Six kinase subunits can be modeled to bind the assembled hexamer without collision, and therefore this CksHs2 hexamer may part icipate in cell cycle control by acting as the hub for Cdk multimeriza tion in vivo.