Sandbox Reserved 826: Difference between revisions

CDK4 in complex with Cyclin D1 shows an engagement of the CDK4 alpha-helix with cyclin D1. Nevertheless, the helix does perform the conformational switch, normally known for CDK activation in other CDK/cyclin complexes <ref> PMID: 7630397 </ref>. Surprisingly, the CDK4/cyclin D1 structure reminds to the structures of inactive structures of non cyclin bound CDK2 and CDK7 <ref> PMID: 8510751 </ref>. Further stabilization of the CDK4 T-loop in the inactive confirmation is achieved by interactions of C- and N- terminal lobes of the kinase. These residues, containing an <scene name='56/568024/Dfg_motif/1'>Asp158–Phe159–Gly160</scene> (DFG) motif are condensed into a helix, which is stabilized by interactions with the alpha-C-helix, ß4-strand, ß6-strand as well as the apex of the T-loop. The architecture of the T-Loop is similar to the one observed at CDK7 and CDK6. CDK4 kinase activation could be achieved due to movement of the alpha-C-helix. Although the C-alpha-lobe of CDK4 seems to be bound by Cyclin D1, the rotation of the C-lobe of CDK4 is not maximal. This reduces the buried surface area of of the CDK4/cyclin D1 interface in comparison of the buried surface of other CDK/cyclin complexes.