Naturally evolved G protein-coupled receptors adopt metastable conformations

Naturally evolved G protein-coupled receptors adopt metastable conformations.

A wide range of membrane receptors signal through conformational changes, and the resulting protein conformational flexibility often hinders their structural studies. Because the determinants of membrane receptor conformational stability are still poorly understood, identifying a minimal set of perturbations stabilizing a membrane protein in a given conformation remains a major challenge in mem...

Eukaryotic G protein signaling evolved to require G protein-coupled receptors for activation.

Although bioinformatic analysis of the increasing numbers of diverse genome sequences and amount of functional data has provided insight into the evolution of signaling networks, bioinformatics approaches have limited application for understanding the evolution of highly divergent protein families. We used biochemical analyses to determine the in vitro properties of selected divergent component...

G Protein-coupled receptors

G protein-coupled receptors and heterotrimeric G proteins can diffuse laterally in the plasma membrane such that one receptor can catalyze the activation (GDP/GTP exchange) of multiple G proteins. In some cases, these processes are fast enough to support molecular signal amplification, where a single receptor maintains the activation of multiple G proteins at steady-state. Amplification in cell...

G-protein-coupled receptors.

G-Protein-coupled receptors mediate many of the hypnotic and analgesic actions of the drugs employed in anesthesia. Notably, opioid agonists represent the most successful and efficacious class of analgesic agents employed over the last century. Also, major clinical advances have been made by the study of alpha(2) adrenoceptor agonists, which possess both hypnotic and analgesic qualities that ar...

Modelling G protein-coupled receptors