Fig. 1: Overall structure of the GPR103–mini-G_sqiβ₁γ₂–scFv16–Nb35 complex.

a Amino acid sequences of QRFP43 and QRFP26. b Cryo-EM density map of the GPR103–mini-G_sqiβ₁γ₂–scFv16–Nb35 individually colored. c Refined structures of the complex are shown as a ribbon representation. d Diagram of GPR103. N-terminal forms a helix-loop-helix motif. ECL2 forms a long β-sheet. e Ribbon representation of the QRFP26 and GPR103. Density focused on QRFP26 (pink). Two disulfide bonds are represented by stick models. The one is the highly conserved disulfide bond between C118^3.25 and C201^ECL2, and the other is atypical disulfide bond between C285^6.47 and C327^7.48. The C118^3.25A and C201^ECL2A mutations abolished the QRFP26 potency (Supplementary Fig. 1a–d). By contrast, the C285^6.47A and C327^7.48A mutations did not alter the potency, indicating their lesser importance for receptor function.