8S30

Crystal structure of human PLK1 Polo-Box Domain in complex with Mis18

8S30 の概要

• エントリーDOI: 10.2210/pdb8s30/pdb
• 分子名称: Serine/threonine-protein kinase PLK1, Protein Mis18-alpha (3 entities in total)
• 機能のキーワード: plk1, mis18 complex, centromere, chromosome missegregation, cell cycle
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28756.71

構造登録者

Jeyaprakash, A.A.,Medina-Pritchard, B. (登録日: 2024-02-19, 公開日: 2024-08-21, 最終更新日: 2024-11-13)

主引用文献

Parashara, P.,Medina-Pritchard, B.,Abad, M.A.,Sotelo-Parrilla, P.,Thamkachy, R.,Grundei, D.,Zou, J.,Spanos, C.,Kumar, C.N.,Basquin, C.,Das, V.,Yan, Z.,Al-Murtadha, A.A.,Kelly, D.A.,McHugh, T.,Imhof, A.,Rappsilber, J.,Jeyaprakash, A.A.
PLK1-mediated phosphorylation cascade activates Mis18 complex to ensure centromere inheritance.
Science, 385:1098-1104, 2024

PubMed Abstract: Accurate chromosome segregation requires the attachment of microtubules to centromeres, epigenetically defined by the enrichment of CENP-A nucleosomes. During DNA replication, CENP-A nucleosomes undergo dilution. To preserve centromere identity, correct amounts of CENP-A must be restored in a cell cycle-controlled manner orchestrated by the Mis18 complex (Mis18α-Mis18β-Mis18BP1). We demonstrate here that PLK1 interacts with the Mis18 complex by recognizing self-primed phosphorylations of Mis18α (Ser) and Mis18BP1 (Thr and Ser) through its Polo-box domain. Disrupting these phosphorylations perturbed both centromere recruitment of the CENP-A chaperone HJURP and new CENP-A loading. Biochemical and functional analyses showed that phosphorylation of Mis18α and PLK1 binding were required to activate Mis18α-Mis18β and promote Mis18 complex-HJURP interaction. Thus, our study reveals key molecular events underpinning the licensing role of PLK1 in ensuring accurate centromere inheritance.

PubMed: 39236175
DOI: 10.1126/science.ado8270

実験手法

X-RAY DIFFRACTION (1.94 Å)