7LFH
Cryo-EM structure of NLRP3 double-ring cage, 6-fold (12-mer)
Summary for 7LFH
| Entry DOI | 10.2210/pdb7lfh/pdb |
| EMDB information | 23302 23303 23304 23305 |
| Descriptor | NACHT, LRR and PYD domains-containing protein 3 (1 entity in total) |
| Functional Keywords | nlrp3, nek7, nucleotid-binding, atp-binding, inflammasome, immunity, innate immunity, nacht, lrr, pyd, immune system |
| Biological source | Mus musculus (house mouse) |
| Total number of polymer chains | 12 |
| Total formula weight | 1425626.63 |
| Authors | Andreeva, L.,Rawson, S.,Wu, H. (deposition date: 2021-01-17, release date: 2021-12-15, Last modification date: 2024-05-29) |
| Primary citation | Andreeva, L.,David, L.,Rawson, S.,Shen, C.,Pasricha, T.,Pelegrin, P.,Wu, H. NLRP3 cages revealed by full-length mouse NLRP3 structure control pathway activation. Cell, 184:6299-, 2021 Cited by PubMed Abstract: The NACHT-, leucine-rich-repeat- (LRR), and pyrin domain-containing protein 3 (NLRP3) is emerging to be a critical intracellular inflammasome sensor of membrane integrity and a highly important clinical target against chronic inflammation. Here, we report that an endogenous, stimulus-responsive form of full-length mouse NLRP3 is a 12- to 16-mer double-ring cage held together by LRR-LRR interactions with the pyrin domains shielded within the assembly to avoid premature activation. Surprisingly, this NLRP3 form is predominantly membrane localized, which is consistent with previously noted localization of NLRP3 at various membrane organelles. Structure-guided mutagenesis reveals that trans-Golgi network dispersion into vesicles, an early event observed for many NLRP3-activating stimuli, requires the double-ring cages of NLRP3. Double-ring-defective NLRP3 mutants abolish inflammasome punctum formation, caspase-1 processing, and cell death. Thus, our data uncover a physiological NLRP3 oligomer on the membrane that is poised to sense diverse signals to induce inflammasome activation. PubMed: 34861190DOI: 10.1016/j.cell.2021.11.011 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.2 Å) |
Structure validation
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