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Fig. 30.3. The structure of the vCYC (purple), CDK6 (cyan), p18Inkb (yellow) complex from side (a) and top (b) views, compared to cellular cyclin A (purple), CDK2 (cyan) side (c) and top (d) views.

Fig. 30.3

The structure of the vCYC (purple), CDK6 (cyan), p18Inkb (yellow) complex from side (a) and top (b) views, compared to cellular cyclin A (purple), CDK2 (cyan) side (c) and top (d) views. Unlike cellular cyclins, the regulatory T-loop of CDK6 is excluded from interaction with vCYC but the PSTAIRE regulatory helix of CDK6 still forms an interface with vCYC. The PSTAIRE helix forms part of the ATP binding domain required for kinase activity while the T loop acts as a negative regulator of kinase activity and must be phosphorylated by cyclin-activating kinases (CAK) in cellular cyclin–CDK complexes. While CAK phosphorylation may enhance vCYC-CDK6 stability, displacement of the T loop by vCYC allows this complex to be active in the absence of CAK activity. The structure of vCYC-CDK6 also reveals loss of the binding pocket used by cyclin-dependent kinase inhibitors (CDKI) of the CIP1/KIP1 family. These and other features support experimental data showing the vCYC-CDK6 not only have a broader target range than cellular D-type cyclins but also escape many normal negative regulatory controls imposed on the cellular cyclin machinery. Reprinted with permission (Jeffrey et al., 2000). (See color plate section.)

Image 9780521827140psl_fig018

From: Chapter 30, KSHV manipulation of the cell cycle and apoptosis

Cover of Human Herpesviruses
Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis.
Arvin A, Campadelli-Fiume G, Mocarski E, et al., editors.
Cambridge: Cambridge University Press; 2007.
Copyright © Cambridge University Press 2007.

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