PMC

Longitudinal sections, ultrathin of specimen #542 (a, b) and semithin of specimen #675 (c, d). a Prostomium anterior to peristomium with prototroch (pr), tentacle (te), foregut (fg), and midgut (mg) with adjacent ventral blood vessel (vv); b prostomium with unpaired coelomic cavity (cp) anterior to peristomium with prototroch (pr) and mouth opening (mo), segment 1 with tentacle (te), foregut (fg), and midgut (mg); c prostomium and peristomium with mouth opening (mo), segment 1 with tentacle (te), foregut (fg) with adjacent dorsal (dv) and ventral blood vessel (vv), midgut (mg), trophosome (tr), and coelomic cavity (c1); segment 2 with coelomic cavity (c2); d prostomium with coelomic cavity (cp), segment 1 with tentacle (te), trophosome (tr), midgut (mg), and coelomic cavity (c1)

Structural details of TR. a, overall structure of TR shown in ribbon representation. Transmembrane α-helices A–G are shown in pink, interhelical loops in the cytoplasmic (CP) and extracellular (EC) sides of the membrane are shown in gray, and β-strands in the BC loop are shown in blue. All-trans-retinal connected to Lys²³³ via a protonated Schiff base linkage is shown as a yellow stick. b, superimposed structures of TR (pink) and XR () (white; PDB ID: 3DDL) and TR and BR () (white; PDB ID: 1C3W). r.m.s.d. values were calculated using carbonyl carbon. Magnified views of the retinal chromophore are shown below. c, expected carotenoid-binding cavity in TR. The carotenoid SX in the XR structure () is superimposed on the E- and F-helices in the TR structure. The magnified view shows the geometry between SX in XR and the all-trans-retinal in TR. The amino acid sequence alignments of the E- and F-helices are shown at the bottom of the panel. The residues involved in carotenoid binding in XR are conserved in the TR sequence (bold red letters). The most important Gly residue is conserved in TR as Gly¹⁵². d, putative proton transport pathway in TR. The retinal and residues involved in proton transport are shown in stick representation.

A, BFACS analysis of neutrophil numbers (A) or ELISA (B) of IL‐1β in the peritoneal cavity of 10‐week‐old male C57BL/6J mice intraperitoneally injected with MSU (1 mg/mouse) with or without TR (200 mg/kg of body weight). n = 8 per group.C, DTime course of changes of joint swelling (C) or ELISA (D) of IL‐1β in the supernatants of joint culture of 10‐week‐old male WT or Nlrp3 ^−/− mice intra‐articularly injected with MSU with or without oral TR administration (200 mg/kg of body weight). n = 6 per group.E Nlrp3A ^350VneoR crossed with LysM‐Cre mice (NLRP3‐mut) treated with vehicle or TR at day 9.FWeight of wild‐type mice or Nlrp3A ^350VneoR crossed with LysM‐Cre mice (NLRP3‐mut) treated with vehicle or TR at day 9. For WT vehicle and WT TR, n = 6; NLRP3‐mut PBS n = 4; and NLRP3‐mut TR n = 8.GSurvival of NLRP3‐mut mice treated with vehicle or TR up to day 18. TR group n = 8, vehicle group n = 7.Data information: Data are shown as mean and s.e.m. and are representative of two or three independent experiments. Statistics were analyzed using an unpaired Student's t‐test or a generalized Wilcoxon test (G): *P < 0.05, ***P < 0.001, NS, not significant.

The figure shows the overlay of TR in complex with compound 1 (magenta, pdb code: 6RB5) and other tworepresentative inhibitors: cyclohexylpirrolidine derivative (green, pdb code:4NEV) [Persch 2014] and dihydroquinazoline (orange, pdb: 2WP6) [].