Three-dimensional structure of human cyclin H, a positive regulator of the CDK-activating kinase

Nat Struct Biol. 1996 Oct;3(10):849-55. doi: 10.1038/nsb1096-849.

Abstract

Cyclin-dependent kinases (CDKs), which play a key role in cell cycle control, are activated by the CDK activating kinase (CAK), which activates cyclin-bound CDKs by phosphorylation at a specific threonine residue. Vertebrate CAK contains two key components: a kinase subunit with homology to its substrate CDKs and a regulatory subunit with homology to cyclins. We have determined the X-ray crystal structure of the regulatory subunit of CAK, cyclin H, at 2.6 A resolution. Cyclin H contains two alpha-helical core domains with a fold similar to that of cyclin A, a regulatory subunit of CAK substrate CDK2, and of TFIIB, a transcription factor. Outside of the core domains, the N- and C-terminal regions of the three structures are completely different. The conformational differences between cyclin H and A structures may reflect functional differences between the two cyclins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Cloning, Molecular
  • Cyclin H
  • Cyclin-Dependent Kinases*
  • Cyclins / chemistry*
  • Cyclins / genetics
  • Cyclins / metabolism
  • Humans
  • Molecular Sequence Data
  • Protein Folding
  • Protein-Serine-Threonine Kinases / metabolism*
  • Sequence Alignment
  • Sequence Analysis

Substances

  • CCNH protein, human
  • Cyclin H
  • Cyclins
  • Protein-Serine-Threonine Kinases
  • Cyclin-Dependent Kinases
  • cyclin-dependent kinase-activating kinase