9FH9

Structure of CyclinB1 N-terminus bound to the NCP

9FH9 の概要

• エントリーDOI: 10.2210/pdb9fh9/pdb
• EMDBエントリー: 50443
• 分子名称: G2/mitotic-specific cyclin-B1, Histone H3.1, Histone H4, ... (8 entities in total)
• 機能のキーワード: arginine anchor, ncp, cyclin b1, complex, cell cycle
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 204842.70

構造登録者

Young, R.V.C.,Muhammad, R.,Alfieri, C. (登録日: 2024-05-27, 公開日: 2024-07-24, 最終更新日: 2024-10-16)

主引用文献

Cirillo, L.,Young, R.,Veerapathiran, S.,Roberti, A.,Martin, M.,Abubacar, A.,Perosa, C.,Coates, C.,Muhammad, R.,Roumeliotis, T.I.,Choudhary, J.S.,Alfieri, C.,Pines, J.
Spatial control of the APC/C ensures the rapid degradation of cyclin B1.
Embo J., 43:4324-4355, 2024

PubMed Abstract: The proper control of mitosis depends on the ubiquitin-mediated degradation of the right mitotic regulator at the right time. This is effected by the Anaphase Promoting Complex/Cyclosome (APC/C) ubiquitin ligase that is regulated by the Spindle Assembly Checkpoint (SAC). The SAC prevents the APC/C from recognising Cyclin B1, the essential anaphase and cytokinesis inhibitor, until all chromosomes are attached to the spindle. Once chromosomes are attached, Cyclin B1 is rapidly degraded to enable chromosome segregation and cytokinesis. We have a good understanding of how the SAC inhibits the APC/C, but relatively little is known about how the APC/C recognises Cyclin B1 as soon as the SAC is turned off. Here, by combining live-cell imaging, in vitro reconstitution biochemistry, and structural analysis by cryo-electron microscopy, we provide evidence that the rapid recognition of Cyclin B1 in metaphase requires spatial regulation of the APC/C. Using fluorescence cross-correlation spectroscopy, we find that Cyclin B1 and the APC/C primarily interact at the mitotic apparatus. We show that this is because Cyclin B1, like the APC/C, binds to nucleosomes, and identify an 'arginine-anchor' in the N-terminus as necessary and sufficient for binding to the nucleosome. Mutating the arginine anchor on Cyclin B1 reduces its interaction with the APC/C and delays its degradation: cells with the mutant, non-nucleosome-binding Cyclin B1 become aneuploid, demonstrating the physiological relevance of our findings. Together, our data demonstrate that mitotic chromosomes promote the efficient interaction between Cyclin B1 and the APC/C to ensure the timely degradation of Cyclin B1 and genomic stability.

PubMed: 39143240
DOI: 10.1038/s44318-024-00194-2

実験手法

ELECTRON MICROSCOPY (2.5 Å)