Extended Data Figure 6 |. Evolutionary coupling analysis of RXFP1.

a, Evolutionary couplings for RXFP1 residues 405–689 (black) compared to the active-state structure contacts (green) show close agreement between predicted contacts from ECs and the cryo-EM model. b, Evolutionary couplings for RXFP1 residues 120–757 (black) compared to the active-state 7TM structure and LRR AlphaFold2²⁷ model contacts (blue), highlighting ECL2 evolutionary couplings that provide insight into two potential loop conformations in magenta (T559^ECL2–Ile396, Gly561^ECL2–Ser397, Phe564^ECL2–Ile396, Phe564^ECL2–Val666^7.38). c, Diagram of RXFP1 domains. Stars indicate regions of RXFP1 containing residues with the highest scoring ECs with ECL2, TM7 and the hinge region. d, The Phe564^ECL2 and Val666^7.38 residues from evolutionary coupling analysis are in close contact in the RXFP1 active-state structure.