7RL3

Structure of Drosophila melanogaster Plk4 PB3

Summary for 7RL3

• Entry DOI: 10.2210/pdb7rl3/pdb
• Descriptor: Serine/threonine-protein kinase PLK4 (2 entities in total)
• Functional Keywords: kinase, sak kinase, plk4, polo box, signaling protein, transferase
• Biological source: Drosophila melanogaster (Fruit fly)
• Total number of polymer chains: 2
• Total formula weight: 19864.63

Authors

Slep, K.C.,Slevin, L.K. (deposition date: 2021-07-23, release date: 2022-08-03, Last modification date: 2023-08-16)

Primary citation

Ryniawec, J.M.,Buster, D.W.,Slevin, L.K.,Boese, C.J.,Amoiroglou, A.,Dean, S.M.,Slep, K.C.,Rogers, G.C.
Polo-like kinase 4 homodimerization and condensate formation regulate its own protein levels but are not required for centriole assembly.
Mol.Biol.Cell, 34:ar80-ar80, 2023

PubMed Abstract: Polo-like kinase 4 (Plk4) is the master-regulator of centriole assembly, and cell cycle-dependent regulation of its activity maintains proper centrosome number. During most of the cell cycle, Plk4 levels are nearly undetectable due to its ability to autophosphorylate and trigger its own ubiquitin-mediated degradation. However, during mitotic exit, Plk4 forms a single aggregate on the centriole surface to stimulate centriole duplication. Whereas most Polo-like kinase family members are monomeric, Plk4 is unique because it forms homodimers. Notably, Plk4 -autophosphorylates a degron near its kinase domain, a critical step in autodestruction. While it is thought that the purpose of homodimerization is to promote -autophosphorylation, this has not been tested. Here, we generated separation-of-function Plk4 mutants that fail to dimerize and show that homodimerization creates a binding site for the Plk4 activator, Asterless. Surprisingly, however, Plk4 dimer mutants are catalytically active in cells, promote centriole assembly, and can -autophosphorylate through concentration-dependent condensate formation. Moreover, we mapped and then deleted the weak-interacting regions within Plk4 that mediate condensation and conclude that dimerization and condensation are not required for centriole assembly. Our findings suggest that Plk4 dimerization and condensation function simply to down-regulate Plk4 and suppress centriole overduplication.

PubMed: 37163316
DOI: 10.1091/mbc.E22-12-0572

Experimental method

X-RAY DIFFRACTION (1.75 Å)