Three "hotspots" important for adenosine A(2B) receptor activation: a mutational analysis of transmembrane domains 4 and 5 and the second extracellular loop.

ABSTRACT: G protein-coupled receptors (GPCRs) are a major drug target and can be activated by a range of stimuli, from photons to proteins. Despite the progress made in the last decade in molecular and structural biology, their exact activation mechanism is still unknown. Here we describe new insights in specific regions essential in adenosine A(2B) receptor activation (A(2B)R), a typical class A GPCR. We applied unbiased random mutagenesis on the middle part of the human adenosine A(2B)R, consisting of transmembrane domains 4 and 5 (TM4 and TM5) linked by extracellular loop 2 (EL2), and subsequently screened in a medium-throughput manner for gain-of-function and constitutively active mutants. For that purpose, we used a genetically engineered yeast strain (Saccharomyces cerevisiae MMY24) with growt

SUBMITTER: Peeters MC 

PROVIDER: S-EPMC3286537 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature