Human CksHs2 atomic structure: a role for its hexameric assembly in cell cycle control.
The cell cycle regulatory protein CksHs2 binds to the catalytic subunit of the cyclin-dependent kinases (Cdk's) and is essential for their biological function. The crystal structure of the protein was determined at 2.1 A resolution. The CksHs2 structure is an unexpected hexamer formed by the symmetric assembly of three interlocked dimers into an unusual 12-stranded beta barrel fold that may represent a prototype for this class of protein structures. Sequence-conserved regions form the unusual beta strand exchange between the subunits of the dimer, and the metal and anion binding sites associated with the hexamer assembly. The two other sequence-conserved regions line a 12 A diameter 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 participate in cell cycle control by acting as the hub for Cdk multimerization in vivo.
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The Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.
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Murtari
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Reed
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Tainer
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D000595:Amino Acid Sequence; D001665:Binding Sites; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins / Q000737:chemistry* / Q000502:physiology; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D003196:Computer Graphics; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D011494:Protein Kinases / Q000378:metabolism; D017433:Protein Structure, Secondary; D016415:Sequence Alignment
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D046911:Macromolecular Substances; D011494:Protein Kinases; D042846:CDC2-CDC28 Kinases; C083689:CKS2 protein, human