Molecular anatomy of PLK1 master docking motifs

Ren, L.; Gasper, R.; Pesenti, M. E.; Janning, P.; Mueller, F.; Koerner, C.; Geue, P.; Wohlgemuth, S.; Esposito Verza, A.; Vetter, I. R.; Musacchio, A.

doi:10.1101/2025.03.28.645803

bioRxiv · 10.1101/2025.03.28.645803

Molecular anatomy of PLK1 master docking motifs

Ren, L.·Gasper, R.·Pesenti, M. E.·Janning, P.·Mueller, F.·Koerner, C.·Geue, P.·Wohlgemuth, S.·Esposito Verza, A.·Vetter, I. R.·Musacchio, A.

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Abstract

The Polo-box domain (PBD) localizes Polo-like kinase 1 (PLK1) near mitotic substrates required for chromosome biorientation. Recent work on mitotic kinetochores showed PLK1 docking begins hierarchically at master docking motifs on BUB1 and CENP-U. Whether master docking motifs have common molecular features remains poorly understood. Presence on CENP-U of two neighbouring motifs generated by initial CDK1 priming and subsequent PLK1 phosphorylation led us to hypothesize PBD dimerization might be involved. Using biochemical, biophysical, and modelling approaches, we gathered strong evidence that CENP-U contains a single master docking motif. The motif is very high affinity and sufficient to form extensive interactions with the PBD, engaging multiple pockets on its surface without obvious added benefits from dimerization. Comparisons with motifs in BUB1, BUBR1, and PRC1 suggests apparent commonalities of master PLK1 docking motifs. We discuss the implications of our observations for the mechanism of PLK1 activation.

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Ren, L., Gasper, R., Pesenti, M. E., Janning, P., Mueller, F., Koerner, C., Geue, P., Wohlgemuth, S., Esposito Verza, A., Vetter, I. R., Musacchio, A.. 2025-03-28. Molecular anatomy of PLK1 master docking motifs. https://doi.org/10.1101/2025.03.28.645803

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