8ATO
Structure of the giant inhibitor of apoptosis, BIRC6 bound to the regulator SMAC
This is a non-PDB format compatible entry.
Summary for 8ATO
| Entry DOI | 10.2210/pdb8ato/pdb |
| Related | 8ATM |
| EMDB information | 15654 |
| Descriptor | Baculoviral IAP repeat-containing protein 6, Diablo IAP-binding mitochondrial protein (2 entities in total) |
| Functional Keywords | e2/e3 ubiquitin ligase, apoptosis |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 1103528.20 |
| Authors | Dietz, L.,Elliott, P.R. (deposition date: 2022-08-23, release date: 2023-03-08, Last modification date: 2024-07-24) |
| Primary citation | Dietz, L.,Ellison, C.J.,Riechmann, C.,Cassidy, C.K.,Felfoldi, F.D.,Pinto-Fernandez, A.,Kessler, B.M.,Elliott, P.R. Structural basis for SMAC-mediated antagonism of caspase inhibition by the giant ubiquitin ligase BIRC6. Science, 379:1112-1117, 2023 Cited by PubMed Abstract: Certain inhibitor of apoptosis (IAP) family members are sentinel proteins that prevent untimely cell death by inhibiting caspases. Antagonists, including second mitochondria-derived activator of caspases (SMAC), regulate IAPs and drive cell death. Baculoviral IAP repeat-containing protein 6 (BIRC6), a giant IAP with dual E2 and E3 ubiquitin ligase activity, regulates programmed cell death through unknown mechanisms. We show that BIRC6 directly restricts executioner caspase-3 and -7 and ubiquitinates caspase-3, -7, and -9, working exclusively with noncanonical E1, UBA6. Notably, we show that SMAC suppresses both mechanisms. Cryo-electron microscopy structures of BIRC6 alone and in complex with SMAC reveal that BIRC6 is an antiparallel dimer juxtaposing the substrate-binding module against the catalytic domain. Furthermore, we discover that SMAC multisite binding to BIRC6 results in a subnanomolar affinity interaction, enabling SMAC to competitively displace caspases, thus antagonizing BIRC6 anticaspase function. PubMed: 36758106DOI: 10.1126/science.ade8840 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3 Å) |
Structure validation
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