Structures of neurokinin 1 receptor in complex with G <sub>q</sub> and G <sub>s</sub> proteins reveal substance P binding mode and unique activation features
Cristian Thom, Janosch Ehrenmann, Santiago Vacca, Yann Waltenspühl, Jendrik Schöppe, Ohad Medalia, Andreas Plückthun
Abstract
R crystal structures reveal that insurmountable antagonists induce a distinct and long-lasting receptor conformation that sterically blocks SP binding. Together, our structures provide important structural insights into ligand and G protein promiscuity, the lack of basal signaling, and agonist- and antagonist-induced conformations in the neurokinin receptor family.
Topics & Concepts
Substance PTachykinin receptor 1ReceptorChemistryStereochemistryBiochemistryNeuropeptideReceptor Mechanisms and SignalingNeuropeptides and Animal PhysiologyChemical Synthesis and Analysis