Structure of the mediator subunit cyclin C and its implications for CDK8 function.

Sabine Hoeppner; Sonja Baumli; Patrick Cramer

doi:10.1016/j.jmb.2005.05.041

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Structure of the mediator subunit cyclin C and its implications for CDK8 function.

Sabine Hoeppner·Sonja Baumli·Patrick Cramer

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Abstract

Cyclin C binds the cyclin-dependent kinases CDK8 and CDK3, which regulate mRNA transcription and the cell cycle, respectively. The crystal structure of cyclin C reveals two canonical five-helix repeats and a specific N-terminal helix. In contrast to other cyclins, the N-terminal helix is short, mobile, and in an exposed position that allows for interactions with proteins other than the CDKs. A model of the CDK8/cyclin C pair reveals two regions in the interface with apparently distinct roles. A conserved region explains promiscuous binding of cyclin C to CDK8 and CDK3, and a non-conserved region may be responsible for discrimination of CDK8 against other CDKs involved in transcription. A conserved and cyclin C-specific surface groove may recruit substrates near the CDK8 active site. Activation of CDKs generally involves phosphorylation of a loop at a threonine residue. In CDK8, this loop is longer and the threonine is absent, suggesting an alternative mechanism of activation that we discuss based on a CDK8-cyclin C model.

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Amino Acid Sequence Binding Sites Crystallography, X-Ray Cyclin-Dependent Kinase 8 Cyclin-Dependent Kinases Cyclins Protein Binding Protein Conformation Schizosaccharomyces Schizosaccharomyces pombe Proteins Sequence Alignment Journal Article Research Support, Non-U.S. Gov't

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Sabine Hoeppner, Sonja Baumli, Patrick Cramer. 2005-07-29. Structure of the mediator subunit cyclin C and its implications for CDK8 function.. https://doi.org/10.1016/j.jmb.2005.05.041

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