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-Structure paper
タイトル | Structures of BIRC6-client complexes provide a mechanism of SMAC-mediated release of caspases. |
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ジャーナル・号・ページ | Science, Vol. 379, Issue 6637, Page 1105-1111, Year 2023 |
掲載日 | 2023年3月17日 |
著者 | Moritz Hunkeler / Cyrus Y Jin / Eric S Fischer / |
PubMed 要旨 | 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 ...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. |
リンク | Science / PubMed:36758104 |
手法 | EM (単粒子) |
解像度 | 1.98 - 3.44 Å |
構造データ | EMDB-27832, PDB-8e2d: EMDB-27833, PDB-8e2e: EMDB-27834, PDB-8e2f: EMDB-27835, PDB-8e2g: EMDB-27836, PDB-8e2h: EMDB-27837, PDB-8e2i: EMDB-27838, PDB-8e2j: EMDB-27839: Cryo-EM density of BIRC6/casp-3 (clusters) EMDB-27840: Cryo-EM density of BIRC6/casp-7 (clusters) EMDB-27841, PDB-8e2k: |
化合物 | ChemComp-HOH: |
由来 |
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キーワード | LIGASE / Ubiquitin / E3 ligase / Apoptosis / Autophagy / IAP |