Fig. 3.

Mechanistic model for PTHR activation. Upon PTH(1–34) binding, there are two rates of association, a faster one that corresponds to agonist binding to the receptor N-domain and is strictly concentration-dependent, followed by a slower binding step to the receptor J-domain that is coupled to receptor activation. The hormone binds to and stabilizes the R⁰ conformation of PTHR, which in turn locks PTH into a high-affinity complex with the receptor. L PTH, R PTHR, LR ⁰ a high-affinity complex between the ligand and the PTHR, LR*G and LR*G* active states for receptor and G protein state, respectively. Time constants (τ) to accomplish each step are given in seconds