Sandbox Reserved 826: Difference between revisions
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== '''Cyclin D1 structure''' == | == '''Cyclin D1 structure''' == | ||
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<Structure load='56/568024/General_structure/1' size='300' frame='true' align='right' caption='3D structure of CDK4 with cyclin D1 in complex' scene='Insert optional scene name here' /> | |||
== '''Cyclin D1-CDK4 complex''' == | == '''Cyclin D1-CDK4 complex''' == | ||
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 Asp158–Phe159–Gly160 <scene name='56/568024/Dfg_motif/1'>(DFG) motif</scene> 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. | 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 Asp158–Phe159–Gly160 <scene name='56/568024/Dfg_motif/1'>(DFG) motif</scene> 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. | ||
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== '''CDK4 in its biological context''' == | == '''CDK4 in its biological context''' == | ||
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== '''References''' == | == '''References''' == | ||
<references/> | <references/> | ||
== '''Contributors''' == | |||
Florian Schaumburg, Simon Metternich | |||
