Nature Structural Biology pp 177 - 181

Some viruses encode cyclin proteins that can activate cell cycle-regulating kinases and thus disrupt the progression of normal cell cycles. While viral cyclins are known to form complexes with these protein kinases, it is not clear how they specifically recognize and activate their substrates. A paper in the March issue of Nature Structural Biology reports the structure of such a complex, which may provide clues to how viral cyclins interact with specific cell cycle-regulating kinases.

Ursula Schulze-Gahmen at E.O. Lawrence Berkley National Laboratory in Berkley, California, USA, and Sung-Hou Kim at the University of California at Berkley, have determined the structure of a complex of cyclin from herpesvirus saimiri with primate cyclin-dependent kinase 6 (CDK6) using X-ray crystallography. The structure reveals that the viral cyclin (Vcyclin) is capable of interacting with CDK6 in much the same way that another kinase, CDK2, interacts with its natural substrate, cyclinA. However the CDK6-Vcyclin complex has a 20% greater contact area between proteins, which may explain the stability of the complex. These results confirm the accepted view of normal cyclin-dependent kinase activation, and suggest a structural basis for the specificity of Vcyclin for CDK6.