Helix 8 is the essential structural motif of mechanosensitive GPCRs.

ABSTRACT: G-protein coupled receptors (GPCRs) are versatile cellular sensors for chemical stimuli, but also serve as mechanosensors involved in various (patho)physiological settings like vascular regulation, cardiac hypertrophy and preeclampsia. However, the molecular mechanisms underlying mechanically induced GPCR activation have remained elusive. Here we show that mechanosensitive histamine H₁ receptors (H₁Rs) are endothelial sensors of fluid shear stress and contribute to flow-induced vasodilation. At the molecular level, we observe that H₁Rs undergo stimulus-specific patterns of conformational changes suggesting that mechanical forces and agonists induce distinct active receptor conformations. GPCRs lacking C-terminal helix 8 (H8) are not mechanosensitive, and tr

SUBMITTER: Erdogmus S 

PROVIDER: S-EPMC6923424 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature