Stabilization of the human beta2-adrenergic receptor TM4-TM3-TM5 helix interface by mutagenesis of Glu122(3.41), a critical residue in GPCR structure.

ABSTRACT: G protein-coupled receptor (GPCR) instability represents one of the most profound obstacles in the structural study of GPCRs that bind diffusible ligands. The introduction of targeted mutations at nonconserved residues that lie proximal to helix interfaces has the potential to enhance the fold stability of the receptor helix bundle while maintaining wild-type receptor function. To test this hypothesis, we studied the effect of amino acid substitutions at Glu122(3.41) in the well-studied beta(2)-adrenergic receptor (beta(2)AR), which was predicted from sequence conservation to lie at a position equivalent to a tryptophan residue in rhodopsin at the 3,4,5 helix interface among transmembrane (TM) domains 3, 4, and 5. Replacement of Glu122(3.41) with bulky hydrophobic residues, such as tryptop

SUBMITTER: Roth CB 

PROVIDER: S-EPMC2292833 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature