3qy2

Publication Abstract from PubMed

Cks (cyclin-dependent kinase subunit) proteins are essential eukaryotic cell cycle regulatory proteins that physically associate with cyclin-dependent kinases (Cdks) to modulate their activity. Cks proteins have also been studied for their ability to form domain-swapped dimers by exchanging beta-strands. Domain swapping is mediated by a conserved beta-hinge region containing two proline residues. Previous structural studies indicate that Cks in its dimer form is unable to bind Cdk, suggesting that the monomer-dimer equilibrium of Cks may have an effect on Cks-mediated Cdk regulation. We present the crystal structure of a proline-to-alanine mutant Saccharomyces cerevisiae Cks protein (Cks1 P93A) that preferentially adopts the monomer conformation but surprisingly fails to bind Cdk. Comparison of the Cks1 P93A structure to that of other Cks proteins reveals that Pro93 is critical for stabilizing a multiple beta-turn structure in the hinge region that properly positions an essential Cdk-binding residue. Additionally, we find that these beta-turn formations, conserved in Cks homologs, have implications for the mechanism and preferentiality of strand exchange. Together, our observations suggest that the conservation of Cks hinge-region prolines reflects their functions in forming a Cdk binding interface and that the ability of these prolines to control partitioning between monomer and dimer is a consequence of the beta-turn networks within the hinge.

The Structure of a Monomeric Mutant Cks Protein Reveals Multiple Functions for a Conserved Hinge-Region Proline.,Balog ER, Saetern OC, Finch W, Hoeft CO, Thai V, Harvey SL, Kellogg DR, Rubin SM J Mol Biol. 2011 Jun 17. PMID:21704044^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.