Extended Data Fig. 3: Sequence and structural analysis of FIIND.

a, ClustalW multiple sequence alignment between human NLRP1 (hNLRP1), mouse NLRP1 (mNLRP1, different isoforms) and rat NLRP1 (rNLRP1, different isoforms). COP, Copenhagen; ZUC, Zucker; LEW, Lewis; SD, Sprague Dawley; and CDF, Fischer. Secondary structures and residue numbers are denoted on the basis of the human FIIND^A structure in the NLRP1–DPP9 ternary complex. Interface residues in the NLRP1–DPP9 complex are annotated with asterisks, and residues in the catalytic triad (H1186, E1195 and S1213) are boxed in black. b, FIIND^A overview with ZU5 (blue) and UPA (light pink) subdomains. The catalytic triad residues (H1186, E1195 and S1213) are shown in sticks. c, Topology of the FIIND with secondary structures labelled. d, Superimposition of FIIND^A onto the UPA^B. NLRP1^B must be free NLRP1 CT, because a ZU5 subdomain at site B would have clashed with ZU5 and UPA at site A and with DPP9. e, The ZU5^A–UPA^A–UPA^B module that binds DPP9. UPA^A and UPA^B interact with each other in a front-to-back manner, with only a 9° rotation between them. f, Altered conformation of the UPA^B N terminus that binds in the DPP9 active-site tunnel in comparison to UPA^A in a complete FIIND^A.