5V3R

CHMP4C in complex with ALIX BRO1

5V3R の概要

• エントリーDOI: 10.2210/pdb5v3r/pdb
• 関連するPDBエントリー: 3C3R 5V3K
• 分子名称: Programmed cell death 6-interacting protein, Charged multivesicular body protein 4c (3 entities in total)
• 機能のキーワード: cell division, transport protein, abscission checkpoint
• 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: 44753.83

構造登録者

Wenzel, D.M.,Alam, S.L.,Sundquist, W.I. (登録日: 2017-03-08, 公開日: 2018-09-12, 最終更新日: 2023-10-04)

主引用文献

Sadler, J.B.A.,Wenzel, D.M.,Williams, L.K.,Guindo-Martinez, M.,Alam, S.L.,Mercader, J.M.,Torrents, D.,Ullman, K.S.,Sundquist, W.I.,Martin-Serrano, J.
A cancer-associated polymorphism in ESCRT-III disrupts the abscission checkpoint and promotes genome instability.
Proc. Natl. Acad. Sci. U.S.A., 115:E8900-E8908, 2018

PubMed Abstract: Cytokinetic abscission facilitates the irreversible separation of daughter cells. This process requires the endosomal-sorting complexes required for transport (ESCRT) machinery and is tightly regulated by charged multivesicular body protein 4C (CHMP4C), an ESCRT-III subunit that engages the abscission checkpoint (NoCut) in response to mitotic problems such as persisting chromatin bridges within the midbody. Importantly, a human polymorphism in CHMP4C (rs35094336, CHMP4C) increases cancer susceptibility. Here, we explain the structural and functional basis for this cancer association: The CHMP4C allele unwinds the C-terminal helix of CHMP4C, impairs binding to the early-acting ESCRT factor ALIX, and disrupts the abscission checkpoint. Cells expressing CHMP4C exhibit increased levels of DNA damage and are sensitized to several conditions that increase chromosome missegregation, including DNA replication stress, inhibition of the mitotic checkpoint, and loss of p53. Our data demonstrate the biological importance of the abscission checkpoint and suggest that dysregulation of abscission by CHMP4C may synergize with oncogene-induced mitotic stress to promote genomic instability and tumorigenesis.

PubMed: 30181294
DOI: 10.1073/pnas.1805504115

実験手法

X-RAY DIFFRACTION (1.906 Å)