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Structural basis for CDK6 activation by a virus-encoded cyclin

Nature Structural Biology volume 9, pages 177–181 (2002)Cite this article

Abstract

Cyclin from herpesvirus saimiri (Vcyclin) preferentially forms complexes with cyclin-dependent kinase 6 (CDK6) from primate host cells. These complexes show higher kinase activity than host cell CDKs in complex with cellular cyclins and are resistant to cyclin-dependent inhibitory proteins (CDKIs). The crystal structure of human CDK6–Vcyclin in an active state was determined to 3.1 Å resolution to better understand the structural basis of CDK6 activation by viral cyclins. The unphosphorylated CDK6 in complex with Vcyclin has many features characteristic of cyclinA-activated, phosphorylated CDK2. There are, however, differences in the conformation at the tip of the T-loop and its interactions with Vcyclin. Residues in the N-terminal extension of Vcyclin wrap around the tip of the CDK6 T-loop and form a short β-sheet with the T-loop backbone. These interactions lead to a 20% larger buried surface in the CDK6–Vcyclin interface than in the CDK2–cyclinA complex and are probably largely responsible for the specificity of Vcyclin for CDK6 and resistance of the complex to inhibition by INK-type CDKIs.

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Figure 1: Schematic drawing of the CDK6–Vcyclin complex.
Figure 2: Electron density maps for the CDK6–Vcyclin complex.
Figure 3: Comparison of the CDK6–Vcyclin and CDK2–cyclinA complex interface.

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Acknowledgements

We thank J. Brandsen for his exploratory work on protein expression and purification and E. Berry for helpful discussions. This work was supported by grants from NIH and DOE.

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Authors and Affiliations

  1. Physical Bioscience Division at E. O. Lawrence Berkeley National Laboratory, Berkeley, 94720, California, USA

    Ursula Schulze-Gahmen & Sung-Hou Kim

  2. Department of Chemistry, University of California, Berkeley, 94720, California, USA

    Sung-Hou Kim

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  1. Ursula Schulze-Gahmen
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  2. Sung-Hou Kim
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Correspondence to Ursula Schulze-Gahmen.

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Schulze-Gahmen, U., Kim, SH. Structural basis for CDK6 activation by a virus-encoded cyclin. Nat Struct Mol Biol 9, 177–181 (2002). https://doi.org/10.1038/nsb756

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