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Structural basis for CDK6 activation by a virus-encoded cyclin.

(2002) Nat Struct Biol 9: 177-181

• PubMed: 11828325 Search on PubMed
• DOI: https://doi.org/10.1038/nsb756
• Primary Citation of Related Structures:  
  1JOW


• PubMed 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 A 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 beta-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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Organizational Affiliation: 

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