6GY2

Crystal structure of human Plk1-PBD in complex with WSSSLATPPTLSSpTVLI phosphopeptide from BRCA2

Summary for 6GY2

• Entry DOI: 10.2210/pdb6gy2/pdb
• Descriptor: Serine/threonine-protein kinase PLK1, Phosphopeptide of BRCA2, GLYCEROL, ... (4 entities in total)
• Functional Keywords: phosphorylation, chromosomes alignement, dna repair, cell cycle
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 60158.24

Authors

Miron, S.,Ropars, V.,Zinn-Justin, S. (deposition date: 2018-06-28, release date: 2019-07-10, Last modification date: 2024-10-23)

Primary citation

Ehlen, A.,Martin, C.,Miron, S.,Julien, M.,Theillet, F.X.,Ropars, V.,Sessa, G.,Beaurepere, R.,Boucherit, V.,Duchambon, P.,El Marjou, A.,Zinn-Justin, S.,Carreira, A.
Proper chromosome alignment depends on BRCA2 phosphorylation by PLK1.
Nat Commun, 11:1819-1819, 2020

PubMed Abstract: The BRCA2 tumor suppressor protein is involved in the maintenance of genome integrity through its role in homologous recombination. In mitosis, BRCA2 is phosphorylated by Polo-like kinase 1 (PLK1). Here we describe how this phosphorylation contributes to the control of mitosis. We identify a conserved phosphorylation site at T207 of BRCA2 that constitutes a bona fide docking site for PLK1 and is phosphorylated in mitotic cells. We show that BRCA2 bound to PLK1 forms a complex with the phosphatase PP2A and phosphorylated-BUBR1. Reducing BRCA2 binding to PLK1, as observed in BRCA2 breast cancer variants S206C and T207A, alters the tetrameric complex resulting in unstable kinetochore-microtubule interactions, misaligned chromosomes, faulty chromosome segregation and aneuploidy. We thus reveal a role of BRCA2 in the alignment of chromosomes, distinct from its DNA repair function, with important consequences on chromosome stability. These findings may explain in part the aneuploidy observed in BRCA2-mutated tumors.

PubMed: 32286328
DOI: 10.1038/s41467-020-15689-9

Experimental method

X-RAY DIFFRACTION (3.11 Å)