Extended Data Fig. 6: Receptor:hormone interaction comparisons across the glycoprotein hormone receptor family.
From: Autoantibody mimicry of hormone action at the thyrotropin receptor
a) Comparison of TSHR, FSHR (PDB: 4AY9), and LH/CGR ECD:hormone (PDB: 7FIH) interactions shows the comparable concave binding-interface and lateral-ECD contacts made by GPHα and receptor-specific β subunits. b) Alignment of the GPHR ECDs reveals the variability in modeled poses of hinge-hormone contacts observed in prior GPHR:hormone structures. c) The N-terminal hinge-hormone disulfide-linked alpha helix presents a hydrophobic face to the α-L1 and α-L3 loops of the TR1402 α-chain and is stabilized by multiple phenylalanine contacts in the GPHα and TSHβ chains. C-terminal hinge-region α helix hidden for visualization. d) Comparison of the TSHR and LHCGR (PDB: 7FIH) transmembrane pockets highlights the similarity in the DPPC and the allosteric agonist Org43554 binding sites. TM4/5 and ECL2 not shown. e) Lipid:protein molar ratio comparison between the M22:TSHR:Gs complex and a non-GPHR Class A receptor control. Data points represent individual measurements from technical replicates (n = 3 for non-GPHR control and n = 4 for M22:TSHR:Gs complex) of the ratio of pmol of lipid DPPC per pmol of protein. **P = 0.0088; Unpaired two-tailed t test was used to calculate statistical differences in lipid:protein molar ratios.
