Conformational Plasticity of Human Protease-Activated Receptor 1 upon Antagonist- and Agonist-Binding (Structure)

Spoerri et al. determine the mechanical, kinetic, and energetic properties of the human protease-activated receptor 1 (PAR1) in the unliganded state, active state, and inhibited state. Binding of the native peptide-based agonist SFLLRN or of the synthetic peptide-based antagonist BMS modulates the mechanical stiffness, conformational flexibility, lifetime, and free energy of certain structural regions within PAR1. The insights outline a general framework of how GPCRs stabilize functional states.