Naturally evolved G protein-coupled receptors adopt metastable conformations.

ABSTRACT: 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 membrane protein structure determination. We present a novel approach integrating bioinformatics, computational design and experimental techniques that identifies and stabilizes metastable receptor regions. When applied to the beta1-adrenergic receptor, the method generated 13 novel receptor variants stabilized in the intended inactive state among which two exhibit an apparent thermostability higher tha

SUBMITTER: Chen KY 

PROVIDER: S-EPMC3421219 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature