3-DIMENSIONAL STRUCTURE OF HUMAN CYCLIN-H, A POSITIVE REGULATOR OF THE CDK-ACTIVATING KINASE

Cyclin-dependent kinases (CDKs), which play a key role in cell cycle c ontrol, are activated by the CDK activating kinase (CAK), which activa tes cyclin-bound CDKs by phosphorylation at a specific threonine resid ue. 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 regu latory subunit of CAK, cyclin H, at 2.6 Angstrom 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-termi nal regions of the three structures are completely different. The conf ormational differences between cyclin H and A structures may reflect f unctional differences between the two cyclins.