5J19

phospho-Pon binding-induced Plk1 dimerization

Summary for 5J19

• Entry DOI: 10.2210/pdb5j19/pdb
• Descriptor: Serine/threonine-protein kinase PLK1, Phosphorylated peptide from Partner of Numb, GLYCEROL, ... (4 entities in total)
• Functional Keywords: polo-box domain, cell cycle
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus: P53350
• Total number of polymer chains: 4
• Total formula weight: 57535.17

Authors

Zhu, K.,Shan, Z.,Zhang, L.,Wen, W. (deposition date: 2016-03-29, release date: 2016-06-15, Last modification date: 2024-10-09)

Primary citation

Zhu, K.,Shan, Z.,Zhang, L.,Wen, W.
Phospho-Pon Binding-Mediated Fine-Tuning of Plk1 Activity
Structure, 24:1110-1119, 2016

PubMed Abstract: In Drosophila neuroblasts (NBs), the asymmetrical localization and segregation of the cell-fate determinant Numb are regulated by its adaptor Partner of Numb (Pon) and the cell-cycle kinase Polo. Polo phosphorylates the Pon localization domain, thus leading to its basal distribution together with Numb, albeit through an unclear mechanism. Here, we find that Cdk1 phosphorylates Pon at Thr63, thus creating a docking site for the Polo-box domain (PBD) of Polo-like kinase 1 (Plk1). The crystal structure of the Plk1 PBD/phospho-Pon complex reveals that two phospho-Pon bound PBDs associate to form a dimer of dimers. We provide evidence that phospho-Pon binding-induced PBD dimerization relieves the autoinhibition of Plk1. Moreover, we demonstrate that the priming Cdk1 phosphorylation of Pon is important for sequential Plk1 phosphorylation. Our results not only provide structural insight into how phosphoprotein binding activates Plk1 but also suggest that binding to different phosphoproteins might mediate the fine-tuning of Plk1 activity.

PubMed: 27238966
DOI: 10.1016/j.str.2016.04.012

Experimental method

X-RAY DIFFRACTION (2 Å)