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  • The EMBO Journal (2000) 19, 2877 - 2888
  • doi:10.1093/emboj/19.12.2877

Crystal structure of a big gamma-herpesvirus cyclin–cdk complex

G.L. Card2, P. Knowles1, H. Laman3, N. Jones3,4 and N.Q. McDonald5

  1. Structural Biology, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, Holborn, London WC2A 3PX, UK
  2. Present address: Laboratory of Structural Biology, University of Auckland, Auckland, New Zealand
  3. Gene Expression Laboratories, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, Holborn, London WC2A 3PX, UK
  4. Present address: Paterson Institute for Cancer Research, Christie Hospital, Manchester M20 9BX, UK
  5. Department of Crystallography, Birkbeck College, Malet Street, London WC1E 7HX, UK

Correspondence to:

N.Q. McDonald, E-mail: mcdonald@icrf.icnet.uk

Received 10 March 2000; Accepted 20 April 2000; Revised 20 April 2000

Several gamma-herpesviruses encode proteins related to the mammalian cyclins, regulatory subunits of cyclin-dependent kinases (cdks) essential for cell cycle progression. We report a 2.5 Å crystal structure of a full-length oncogenic viral cyclin from gamma-herpesvirus 68 complexed with cdk2. The viral cyclin binds cdk2 with an orientation different from cyclin A and makes several novel interactions at the interface, yet it activates cdk2 by triggering conformational changes similar to cyclin A. Sequences within the viral cyclin N-terminus lock part of the cdk2 T-loop within the core of the complex. These sequences and others are conserved amongst the viral and cellular D-type cyclins, suggesting that this structure has wider implications for other cyclin–cdk complexes. The observed resistance of this viral cyclin–cdk complex to inhibition by the p27Kip cdk inhibitor is explained by sequence and conformational variation in the cyclin rendering the p27Kip-binding site on the cyclin subunit non-functional.

  • Keywords:

    • cyclin,
    • cyclin-dependent kinase,
    • herpesvirus,
    • p27Kip,
    • structure