Extended Data Fig. 6: Conformational transitions in NLRP3.
From: Structure of the NLRP3 decamer bound to the cytokine release inhibitor CRID3
a, Overlay of NLRP3 (7PZC) from the decamer structure with the NLRP3–NEK7 complex structure (6NPY)15. The proteins were aligned to the NBD-HD1 subdomains. Only the last three repeats of the LRRs are coloured for clarity. The C-terminal lobe of NEK7 (blue) adopts the space in the concave site of the LRR that is occupied in the NLRP3 decamer structure by the acidic loop (red). b, Overlay of NLRP3 from the decamer assembly with NLR family proteins NOD2 (5IRN)18, monomeric NLRC4 (4KXF)19, and the disc-like NLRC4 (3JBL)48 structure. c, Amino acid register shift in HD2 and trLRR between the NLRP3 decamer and the NLRP3–NEK7 structure. Overlay of residues 435–828 between our structure (7PZC, dark grey/coloured) and the NLRP3–NEK7 structure (6NPY, light grey)15 showing WHD, HD1, trLRR and 3 repeats of the cnLRR. There is a shift in the amino acid register starting from position E538 that varies between -12 residues in the first helix of HD2 and +44 residues in the first β-strand of trLRR. The register synchronizes again at L737 at the beginning of the cnLRR domain. Segments are coloured according to the amino acid register shifts.
