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Structure and regulation of the CDK5-p25(nck5a) complex.

Tarricone C, Dhavan R, Peng J, Areces LB, Tsai LH, Musacchio A
Mol Cell 8 657-69 (2001)
Cited: 147 times
EuropePMC logo PMID: 11583627

Abstract

CDK5 plays an indispensable role in the central nervous system, and its deregulation is involved in neurodegeneration. We report the crystal structure of a complex between CDK5 and p25, a fragment of the p35 activator. Despite its partial structural similarity with the cyclins, p25 displays an unprecedented mechanism for the regulation of a cyclin-dependent kinase. p25 tethers the unphosphorylated T loop of CDK5 in the active conformation. Residue Ser159, equivalent to Thr160 on CDK2, contributes to the specificity of the CDK5-p35 interaction. Its substitution with threonine prevents p35 binding, while the presence of alanine affects neither binding nor kinase activity. Finally, we provide evidence that the CDK5-p25 complex employs a distinct mechanism from the phospho-CDK2-cyclin A complex to establish substrate specificity.

Reviews - 1h4l mentioned but not cited (3)

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Articles - 1h4l mentioned but not cited (12)

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