Extended Data Fig. 5: Interactions between PTH^WT His9 side chain and PTHR residues, and comparison with the interactions of the mutant PTH^H9A.

Panels a-e display MD snapshots of PTH^WT-bound receptor, and panel f, those for the mutant H9A-bound receptor. PTH^WT is cyan, and PTHR is green in panels a–e, and PTH^H9A is light pink, and PTHR is hot pink in panel f. MD snapshots of PTH^WT-bound receptor showing different interactions. a, His9 hydrogen bond with Tyr429 (ECL3). b, Hydrogen bonds with Ser355 and Gly357 main chain (ECL2). c, Hydrogen bond with Ser355 side chain (ECL2). d, Aromatic-aromatic interactions between His9 and Tyr429 (ECL3). e, Hydrogen bond with Gln364 (TM5). f, Interactions between PTHR Leu354 and PTH^H9A Ala9 in triplicate simulations. MD snapshots were collected every 10 ns during the last 50 ns of each simulation are aligned by PTHR^TMD (residues 180 to 460).