3G33

Crystal structure of CDK4/cyclin D3

Summary for 3G33

• Entry DOI: 10.2210/pdb3g33/pdb
• Descriptor: Cell division protein kinase 4, CCND3 protein (2 entities in total)
• Functional Keywords: ser/thr protein kinase, cell cycle, phosphorylation, atp-binding, cell division, disease mutation, kinase, nucleotide-binding, phosphoprotein, proto-oncogene, serine/threonine-protein kinase, transferase, cyclin
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P11802
• Total number of polymer chains: 4
• Total formula weight: 136481.09

Authors

Takaki, T.,Echalier, A.,Brown, N.R.,Hunt, T.,Endicott, J.A.,Noble, M.E.M. (deposition date: 2009-02-01, release date: 2009-03-10, Last modification date: 2024-02-21)

Primary citation

Takaki, T.,Echalier, A.,Brown, N.R.,Hunt, T.,Endicott, J.A.,Noble, M.E.
The structure of CDK4/cyclin D3 has implications for models of CDK activation.
Proc.Natl.Acad.Sci.USA, 106:4171-4176, 2009

PubMed Abstract: Cyclin-dependent kinase 4 (CDK4)/cyclin D complexes are expressed early in the G(1) phase of the cell cycle and stimulate the expression of genes required for G(1) progression by phosphorylation of the product of the retinoblastoma gene, pRb. To elaborate the molecular pathway of CDK4 activation and substrate selection we have determined the structure of nonphosphorylated CDK4/cyclin D3. This structure of an authentic CDK/cyclin complex shows that cyclin binding may not be sufficient to drive the CDK active site toward an active conformation. Phosphorylated CDK4/cyclin D3 is active as a pRb kinase and is susceptible to inhibition by p27(Kip1). Unlike CDK2/cyclin A, CDK4/cyclin D3 can be inactivated by treatment with lambda-phosphatase, implying that phosphorylated T172 is accessible to a generic phosphatase while bound to a cyclin. Taken together, these results suggest that the structural mechanism of CDK4/cyclin D3 activation differs markedly from that of previously studied CDK/cyclin complexes.

PubMed: 19237555
DOI: 10.1073/pnas.0809674106

Experimental method

X-RAY DIFFRACTION (3 Å)