8E2F
Cryo-EM structure of N-terminal arm of BIRC6 (from local refinement 2)
Summary for 8E2F
| Entry DOI | 10.2210/pdb8e2f/pdb |
| EMDB information | 27832 27833 27834 27835 27836 27837 27838 27839 27840 27841 |
| Descriptor | Baculoviral IAP repeat-containing protein 6 (1 entity in total) |
| Functional Keywords | ubiquitin, e3 ligase, apoptosis, autophagy, iap, ligase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 534158.31 |
| Authors | Hunkeler, M.,Fischer, E.S. (deposition date: 2022-08-15, release date: 2023-02-15, Last modification date: 2024-06-12) |
| Primary citation | 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 Cited by 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: 36758104DOI: 10.1126/science.ade5750 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.47 Å) |
Structure validation
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