Summary for 6N1H
| Entry DOI | 10.2210/pdb6n1h/pdb |
| EMDB information | 8902 8903 |
| Descriptor | Apoptosis-associated speck-like protein containing a CARD (1 entity in total) |
| Functional Keywords | inflammasome, filament, immunity, signaling protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 16 |
| Total formula weight | 156402.29 |
| Authors | |
| Primary citation | Li, Y.,Fu, T.M.,Lu, A.,Witt, K.,Ruan, J.,Shen, C.,Wu, H. Cryo-EM structures of ASC and NLRC4 CARD filaments reveal a unified mechanism of nucleation and activation of caspase-1. Proc. Natl. Acad. Sci. U.S.A., 115:10845-10852, 2018 Cited by PubMed Abstract: Canonical inflammasomes are cytosolic supramolecular complexes that activate caspase-1 upon sensing extrinsic microbial invasions and intrinsic sterile stress signals. During inflammasome assembly, adaptor proteins ASC and NLRC4 recruit caspase-1 through homotypic caspase recruitment domain (CARD) interactions, leading to caspase-1 dimerization and activation. Activated caspase-1 processes proinflammatory cytokines and Gasdermin D to induce cytokine maturation and pyroptotic cell death. Here, we present cryo-electron microscopy (cryo-EM) structures of NLRC4 CARD and ASC CARD filaments mediated by conserved three types of asymmetric interactions (types I, II, and III). We find that the CARDs of these two adaptor proteins share a similar assembly pattern, which matches that of the caspase-1 CARD filament whose structure we defined previously. These data indicate a unified mechanism for downstream caspase-1 recruitment through CARD-CARD interactions by both adaptors. Using structure modeling, we further show that full-length NLRC4 assembles via two separate symmetries at its CARD and its nucleotide-binding domain (NBD), respectively. PubMed: 30279182DOI: 10.1073/pnas.1810524115 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.17 Å) |
Structure validation
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