Extended Data Fig. 8: The binding pocket of ML-109 in TSHR and structure comparison of TSHR and LHCGR.
From: Hormone- and antibody-mediated activation of the thyrotropin receptor
a, Concentration-response curves for ML-109, TSH, and M22ScFv induced TSHR activation. Data were shown as mean ± S.E.M. from five independent experiments, which performed in triplicates. b, c, Structure comparison of ML-109 binding pocket in the TSH–TSHR–Gs complex with Org43553 binding pocket in the CG–LHCGR–Gs complex. d, Concentration-response curves for ML-109 and CG induced WT and mutated LHCGR activation. Data were shown as mean ± S.E.M. from three independent experiments (n = 3), which performed in triplicates. TM6 means swapping of the extracellular portion of LHCGR TM6 (residues 588-596) with the corresponding TSHR TM6 region (residues 643-651). F515L/A349E/TM6 means mutations of F515L and A349E in addition to the above TM6 mutation. The cAMP data was normalized by CG-induced WT receptor within each individual experiment, with the basal activity for WT as 0, while the fitted Emax of WT as 100. UD, undetectable.
