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Human CDK5-cyclin B1 structures uncover a conserved mitotic CDK activation mechanism

Syed, A.; Arvai, A. S.; Cong, K.; Zheng, X.-F.; Verway-Cohen, A.; Tsai, M.-S.; Nguyen, H.; Bacolla, A.; Tsai, C.-L.; Lantz, G.; Spektor, A.; Chowdhury, D.; Tainer, J. A.

2025-09-12 biochemistry
10.1101/2025.09.10.675329 bioRxiv
Show abstract

Cyclin-dependent kinase 5 (CDK5), long considered atypical and activated by non-cyclin cofactors in neurons, also functions in mitosis. To resolve its activation mechanism during mitosis, we determined the first high-resolution crystal structures of CDK5-cyclin B1 in apo and nucleotide-bound states. Contrary to AlphaFold predictions, we find CDK5 structures unexpectedly mirrors CDK1-cyclin B1 assembly and activation, establishing CDK5 as a bona fide mitotic kinase acting in parallel with CDK1.

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