5FC3

Structural basis of cohesin cleavage by separase

5FC3 の概要

• エントリーDOI: 10.2210/pdb5fc3/pdb
• 関連するPDBエントリー: 5FBY 5FC2
• 関連するBIRD辞書のPRD_ID: PRD_001260
• 分子名称: pAMK peptide, separase (3 entities in total)
• 機能のキーワード: cysteine protease, cohesin, complex, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Chaetomium thermophilum; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 69919.24

構造登録者

Lin, Z.,Luo, X.,Yu, H. (登録日: 2015-12-14, 公開日: 2016-03-30, 最終更新日: 2024-11-06)

主引用文献

Lin, Z.,Luo, X.,Yu, H.
Structural basis of cohesin cleavage by separase
Nature, 532:131-134, 2016

PubMed Abstract: Accurate chromosome segregation requires timely dissolution of chromosome cohesion after chromosomes are properly attached to the mitotic spindle. Separase is absolutely essential for cohesion dissolution in organisms from yeast to man. It cleaves the kleisin subunit of cohesin and opens the cohesin ring to allow chromosome segregation. Cohesin cleavage is spatiotemporally controlled by separase-associated regulatory proteins, including the inhibitory chaperone securin, and by phosphorylation of both the enzyme and substrates. Dysregulation of this process causes chromosome missegregation and aneuploidy, contributing to cancer and birth defects. Despite its essential functions, atomic structures of separase have not been determined. Here we report crystal structures of the separase protease domain from the thermophilic fungus Chaetomium thermophilum, alone or covalently bound to unphosphorylated and phosphorylated inhibitory peptides derived from a cohesin cleavage site. These structures reveal how separase recognizes cohesin and how cohesin phosphorylation by polo-like kinase 1 (Plk1) enhances cleavage. Consistent with a previous cellular study, mutating two securin residues in a conserved motif that partly matches the separase cleavage consensus converts securin from a separase inhibitor to a substrate. Our study establishes atomic mechanisms of substrate cleavage by separase and suggests competitive inhibition by securin.

PubMed: 27027290
DOI: 10.1038/nature17402

実験手法

X-RAY DIFFRACTION (3.1 Å)