8E2G

Cryo-EM structure of N-terminal arm (aa68-966) of BIRC6 (from local refinement 3)

8E2G の概要

• エントリーDOI: 10.2210/pdb8e2g/pdb
• EMDBエントリー: 27832 27833 27834 27835 27836 27837 27838 27839 27840 27841
• 分子名称: Baculoviral IAP repeat-containing protein 6 (1 entity in total)
• 機能のキーワード: ubiquitin, e3 ligase, apoptosis, autophagy, iap, ligase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 534158.31

構造登録者

Hunkeler, M.,Fischer, E.S. (登録日: 2022-08-15, 公開日: 2023-02-15, 最終更新日: 2024-06-12)

主引用文献

Hunkeler, M.,Jin, C.Y.,Fischer, E.S.
Structures of BIRC6-client complexes provide a mechanism of SMAC-mediated release of caspases.
Science, 379:1105-1111, 2023

PubMed Abstract: Tight regulation of apoptosis is essential for metazoan development and prevents diseases such as cancer and neurodegeneration. Caspase activation is central to apoptosis, and inhibitor of apoptosis proteins (IAPs) are the principal actors that restrain caspase activity and are therefore attractive therapeutic targets. IAPs, in turn, are regulated by mitochondria-derived proapoptotic factors such as SMAC and HTRA2. Through a series of cryo-electron microscopy structures of full-length human baculoviral IAP repeat-containing protein 6 (BIRC6) bound to SMAC, caspases, and HTRA2, we provide a molecular understanding for BIRC6-mediated caspase inhibition and its release by SMAC. The architecture of BIRC6, together with near-irreversible binding of SMAC, elucidates how the IAP inhibitor SMAC can effectively control a processive ubiquitin ligase to respond to apoptotic stimuli.

PubMed: 36758104
DOI: 10.1126/science.ade5750

実験手法

ELECTRON MICROSCOPY (2.99 Å)