5FNA
Cryo-EM reconstruction of caspase-1 CARD
Summary for 5FNA
| Entry DOI | 10.2210/pdb5fna/pdb |
| EMDB information | 3241 |
| Descriptor | Caspase-1 (1 entity in total) |
| Functional Keywords | hydrolase, card, inflammasome, filament, signalosome, helical reconstruction, death domain |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 8 |
| Total formula weight | 76721.37 |
| Authors | Li, Y.,Lu, A.,Schmidt, F.I.,Yin, Q.,Chen, S.,Fu, T.M.,Tong, A.B.,Ploegh, H.L.,Mao, Y.,Wu, H. (deposition date: 2015-11-11, release date: 2016-03-30, Last modification date: 2024-05-08) |
| Primary citation | Li, Y.,Lu, A.,Schmidt, F.I.,Yin, Q.,Chen, S.,Fu, T.M.,Tong, A.B.,Ploegh, H.L.,Mao, Y.,Wu, H. Molecular Basis of Caspase-1 Polymerization and its Inhibition by a Novel Capping Mechanism Nat.Struct.Mol.Biol., 23:416-, 2016 Cited by PubMed Abstract: Inflammasomes are cytosolic caspase-1-activation complexes that sense intrinsic and extrinsic danger signals, and trigger inflammatory responses and pyroptotic cell death. Homotypic interactions among Pyrin domains and caspase recruitment domains (CARDs) in inflammasome-complex components mediate oligomerization into filamentous assemblies. Several cytosolic proteins consisting of only interaction domains exert inhibitory effects on inflammasome assembly. In this study, we determined the structure of the human caspase-1 CARD domain (caspase-1(CARD)) filament by cryo-electron microscopy and investigated the biophysical properties of two caspase-1-like CARD-only proteins: human inhibitor of CARD (INCA or CARD17) and ICEBERG (CARD18). Our results reveal that INCA caps caspase-1 filaments, thereby exerting potent inhibition with low-nanomolar Ki on caspase-1(CARD) polymerization in vitro and inflammasome activation in cells. Whereas caspase-1(CARD) uses six complementary surfaces of three types for filament assembly, INCA is defective in two of the six interfaces and thus terminates the caspase-1 filament. PubMed: 27043298DOI: 10.1038/NSMB.3199 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.8 Å) |
Structure validation
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