8AUK

Cryo-EM structure of human BIRC6 in complex with HTRA2.

これはPDB形式変換不可エントリーです。

8AUK の概要

• エントリーDOI: 10.2210/pdb8auk/pdb
• 関連するPDBエントリー: 8ATU 8ATX
• EMDBエントリー: 15672
• 分子名称: Baculoviral IAP repeat-containing protein 6, Serine protease HTRA2, mitochondrial, ZINC ION (3 entities in total)
• 機能のキーワード: e3 ubiquitin ligase, e2/e3 hybrid, inhibitor of apoptosis protein, ligase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 1169154.28

構造登録者

Ehrmann, J.F.,Grabarczyk, D.B.,Clausen, T. (登録日: 2022-08-25, 公開日: 2023-02-15, 最終更新日: 2024-07-24)

主引用文献

Ehrmann, J.F.,Grabarczyk, D.B.,Heinke, M.,Deszcz, L.,Kurzbauer, R.,Hudecz, O.,Shulkina, A.,Gogova, R.,Meinhart, A.,Versteeg, G.A.,Clausen, T.
Structural basis for regulation of apoptosis and autophagy by the BIRC6/SMAC complex.
Science, 379:1117-1123, 2023

PubMed Abstract: Inhibitor of apoptosis proteins (IAPs) bind to pro-apoptotic proteases, keeping them inactive and preventing cell death. The atypical ubiquitin ligase BIRC6 is the only essential IAP, additionally functioning as a suppressor of autophagy. We performed a structure-function analysis of BIRC6 in complex with caspase-9, HTRA2, SMAC, and LC3B, which are critical apoptosis and autophagy proteins. Cryo-electron microscopy structures showed that BIRC6 forms a megadalton crescent shape that arcs around a spacious cavity containing receptor sites for client proteins. Multivalent binding of SMAC obstructs client binding, impeding ubiquitination of both autophagy and apoptotic substrates. On the basis of these data, we discuss how the BIRC6/SMAC complex can act as a stress-induced hub to regulate apoptosis and autophagy drivers.

PubMed: 36758105
DOI: 10.1126/science.ade8873

実験手法

ELECTRON MICROSCOPY (6.2 Å)