8IVQ

Cryo-EM structure of mouse BIRC6, Global map

これはPDB形式変換不可エントリーです。

8IVQ の概要

• エントリーDOI: 10.2210/pdb8ivq/pdb
• EMDBエントリー: 35759
• 分子名称: Isoform 2 of Baculoviral IAP repeat-containing protein 6 (1 entity in total)
• 機能のキーワード: inhibitor of apoptosis protein, birc6, smac, apoptosis
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 1070041.62

構造登録者

Liu, S.,Jiang, T.,Bu, F.,Zhao, J.,Wang, G.,Li, N.,Gao, N.,Qiu, X. (登録日: 2023-03-28, 公開日: 2024-01-24, 最終更新日: 2025-07-23)

主引用文献

Liu, S.S.,Jiang, T.X.,Bu, F.,Zhao, J.L.,Wang, G.F.,Yang, G.H.,Kong, J.Y.,Qie, Y.F.,Wen, P.,Fan, L.B.,Li, N.N.,Gao, N.,Qiu, X.B.
Molecular mechanisms underlying the BIRC6-mediated regulation of apoptosis and autophagy.
Nat Commun, 15:891-891, 2024

PubMed Abstract: Procaspase 9 is the initiator caspase for apoptosis, but how its levels and activities are maintained remains unclear. The gigantic Inhibitor-of-Apoptosis Protein BIRC6/BRUCE/Apollon inhibits both apoptosis and autophagy by promoting ubiquitylation of proapoptotic factors and the key autophagic protein LC3, respectively. Here we show that BIRC6 forms an anti-parallel U-shaped dimer with multiple previously unannotated domains, including a ubiquitin-like domain, and the proapoptotic factor Smac/DIABLO binds BIRC6 in the central cavity. Notably, Smac outcompetes the effector caspase 3 and the pro-apoptotic protease HtrA2, but not procaspase 9, for binding BIRC6 in cells. BIRC6 also binds LC3 through its LC3-interacting region, probably following dimer disruption of this BIRC6 region. Mutation at LC3 ubiquitylation site promotes autophagy and autophagic degradation of BIRC6. Moreover, induction of autophagy promotes autophagic degradation of BIRC6 and caspase 9, but not of other effector caspases. These results are important to understand how the balance between apoptosis and autophagy is regulated under pathophysiological conditions.

PubMed: 38291026
DOI: 10.1038/s41467-024-45222-1

実験手法

ELECTRON MICROSCOPY (3.6 Å)