title: Interactions of cyclins with cyclin-dependent kinases: a common interactive mechanism.
abstract: The formation of cdk-cyclin complexes has been investigated at the molecular level and quantified using spectroscopic approaches. In the absence of phosphorylation, cdk2, cdc2, and cdk7 form highly stable complexes with their "natural" cyclin partners with dissociation constants in the nanomolar range. In contrast, nonphosphorylated cdc2-cyclin H, cdk2-cyclin H, and cdk7-cyclin A complexes present a 25-fold lower stability. On the basis of both the structure of the cdk2-cyclin A complex and on our kinetic results, we suggest that interaction of any cyclin with any cdk involves the same hydrophobic contacts and induces a marked conformational change in the catalytic cleft of the cdks. Although cdks bind ATP strongly, they remain in a catalytically inactive conformation. In contrast, binding of the cyclin induces structural rearrangements which result in the selective reorientation of ATP, a concomitant 3-fold increase in its affinity, and a 5-fold decrease of its release from the active site of cdks.
authors.affiliation: Centre de Recherches de Biochimie Macromoleculaire, CNRS, Montpellier, France.
authors.forename: F
authors.initials: F
authors.lastname: Heitz
authors.forename: M C
authors.initials: MC
authors.lastname: Morris
authors.forename: D
authors.initials: D
authors.lastname: Fesquet
authors.forename: J C
authors.initials: JC
authors.lastname: Cavadore
authors.forename: M
authors.initials: M
authors.lastname: Dorée
authors.forename: G
authors.initials: G
authors.lastname: Divita
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011487:Protein Conformation; D016415:Sequence Alignment; D013050:Spectrometry, Fluorescence; D062367:ortho-Aminobenzoates / Q000378:metabolism
chemical_list: D016213:Cyclins; D046911:Macromolecular Substances; D062367:ortho-Aminobenzoates; C045473:3'-O-(N-methylanthraniloyl) ATP; D000255:Adenosine Triphosphate; D018844:Cyclin-Dependent Kinases