The crystal structure of cyclin A

Structure. 1995 Nov 15;3(11):1235-47. doi: 10.1016/s0969-2126(01)00259-3.

Abstract

Background: Eukaryotic cell cycle progression is regulated by cyclin dependent protein kinases (CDKs) whose activity is regulated by association with cyclins and by reversible phosphorylation. Cyclins also determine the subcellular location and substrate specificity of CDKs. Cyclins exhibit diverse sequences but all share homology over a region of approximately 100 amino acids, termed the cyclin box. From the determination of the structure of cyclin A, together with results from biochemical and genetic analyses, we can identify which parts of the cyclin molecular may contribute to cyclin A structure and function.

Results: We have solved the crystal structure, at 2.0 A resolution, of an active recombinant fragment of bovine cyclin A, cyclin A-3, corresponding to residues 171-432 of human cyclin A. The cyclin box has an alpha-helical fold comprising five alpha helices. This fold is repeated in the C-terminal region, although this region shares negligible sequence similarity with the cyclin box.

Conclusions: Analysis of residues that are conserved throughout the A, B, and E cyclins identifies two exposed clusters of residues, one of which has recently been shown to be involved in the association with human CDK2. The second cluster may identify another site of cyclin A-protein interaction. Comparison of the structure of the unbound cyclin with the structure of cyclin A complexed with CDK2 reveals that cyclin A does not undergo any significant conformational changes on complex formation. Threading analysis shows that the cyclin-box fold is consistent with the sequences of the transcription factor TFIIB and other functionally related proteins. The structural results indicate a role for the cyclin-box fold both as a template for the cyclin family and as a generalised adaptor molecule in the regulation of transcription.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Amino Acid Sequence
  • Animals
  • CDC2-CDC28 Kinases*
  • Cattle
  • Cell Cycle
  • Computer Simulation
  • Crystallography, X-Ray
  • Cyclin A*
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases / metabolism
  • Cyclins / chemistry*
  • Humans
  • Models, Molecular*
  • Molecular Sequence Data
  • Peptide Fragments / chemistry*
  • Protein Binding
  • Protein Conformation*
  • Protein Folding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / metabolism
  • Recombinant Fusion Proteins / chemistry
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Species Specificity
  • Transcription Factor TFIIB
  • Transcription Factors / chemistry
  • Transcription, Genetic

Substances

  • Cyclin A
  • Cyclins
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Transcription Factor TFIIB
  • Transcription Factors
  • cyclin A3 protein, Bos taurus
  • Protein-Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases

Associated data

  • GENBANK/X68321