Loss of constitutive activity is correlated with increased thermostability of the human adenosine A2A receptor.

ABSTRACT:

Background and purpose

Thermostabilization by mutagenesis is one method which has facilitated the determination of high-resolution structures of the adenosine A2A receptor (A(2A)R). Sets of mutations were identified, which both thermostabilized the receptor and resulted in preferential agonist (Rag23 mutant) or antagonist (Rant5 and Rant21) binding forms as assessed by radioligand binding analysis. While the ligand-binding profiles of these mutants are known, the effects these mutations have on receptor activation and downstream signalling are less well characterized.

Experimental approach

Here we have investigated the effects of the thermostabilizing mutations on receptor activation using a yeast cell growth assay. The assay employs an engineered Saccharomyces cerevisiae, M

SUBMITTER: Bertheleme N 

PROVIDER: S-EPMC3696323 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature