Conformational thermostabilization of the beta1-adrenergic receptor in a detergent-resistant form.

ABSTRACT: There are approximately 350 non-odorant G protein-coupled receptors (GPCRs) encoded by the human genome, many of which are predicted to be potential therapeutic targets, but there are only two structures available to represent the whole of the family. We hypothesized that improving the detergent stability of these receptors and simultaneously locking them into one preferred conformation will greatly improve the chances of crystallization. We developed a generic strategy for the isolation of detergent-solubilized thermostable mutants of a GPCR, the beta1-adrenergic receptor. The most stable mutant receptor, betaAR-m23, contained six point mutations that led to an apparent T(m) 21 degrees C higher than the native protein, and, in the presence of bound antagonist, betaAR-m23 was as stable as

SUBMITTER: Serrano-Vega MJ 

PROVIDER: S-EPMC2242685 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature