Supplementary Figure 8: Jansen’s metaphyseal chondrodysplasia–related mutations at the conserved HETX motif result in constitutive PTH1R activation.

a, Extracellular view on the class B conserved HETX motif of superposed PTH1R (green) and activated GLP1R (blue; PDB 5VAI). In the active state receptor, T^6.42 is removed from the network owing to rearrangements in transmembrane helix VI. Residues associated with Jansen’s metaphyseal chondrodysplasia are highlighted in red. b,c, The thermostabilizing mutation I458^7.56A in the crystallized PTH1R and the Jansen’s Metaphyseal Chondrodysplasia-related mutation I458^7.56R facing towards S409^6.41 are located close to the HETX motif (view from the membrane). The bulky side chain of I458^7.56R clashes (indicated by red disks) with helix VI in the inactive receptor state (representative rotamer from PyMOL Mutagenesis Wizard shown).