3QY2

Crystal structure of the P93A monomer mutant of S. cerevisiae Cks1

Summary for 3QY2

• Entry DOI: 10.2210/pdb3qy2/pdb
• Descriptor: Cyclin-dependent kinases regulatory subunit, CITRATE ANION (3 entities in total)
• Functional Keywords: protein kinase activator, ubiquitin binding, transcription, cdc28 kinase, cell cycle, cyclin-dependent kinase, transferase regulator
• Biological source: Saccharomyces cerevisiae (brewer's yeast,lager beer yeast,yeast)
• Total number of polymer chains: 2
• Total formula weight: 27884.18

Authors

Balog, E.R.M.,Saetern, O.C.,Finch, W.,Hoeft, C.O.,Thai, V.,Harvey, S.L.,Kellogg, D.K.,Rubin, S.M. (deposition date: 2011-03-02, release date: 2011-06-29, Last modification date: 2024-02-21)

Primary citation

Balog, E.R.,Saetern, O.C.,Finch, W.,Hoeft, C.O.,Thai, V.,Harvey, S.L.,Kellogg, D.R.,Rubin, S.M.
The structure of a monomeric mutant cks protein reveals multiple functions for a conserved hinge-region proline.
J.Mol.Biol., 411:520-528, 2011

PubMed Abstract: 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 β-strands. Domain swapping is mediated by a conserved β-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 β-turn structure in the hinge region that properly positions an essential Cdk-binding residue. Additionally, we find that these β-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 β-turn networks within the hinge.

PubMed: 21704044
DOI: 10.1016/j.jmb.2011.05.045

Experimental method

X-RAY DIFFRACTION (2.59 Å)