PT  - JOURNAL ARTICLE
AU  - Cheung, A H
AU  - Huang, R R
AU  - Strader, C D
TI  - Involvement of specific hydrophobic, but not hydrophilic, amino acids in the third intracellular loop of the beta-adrenergic receptor in the activation of Gs.
DP  - 1992 Jun 01
TA  - Molecular Pharmacology
PG  - 1061--1065
VI  - 41
IP  - 6
4099  - http://molpharm.aspetjournals.org/content/41/6/1061.short
4100  - http://molpharm.aspetjournals.org/content/41/6/1061.full
SO  - Mol Pharmacol1992 Jun 01; 41
AB  - Mutagenesis and biochemical analysis have indicated that amino acid residues at the amino terminus of the third intracellular loops of guanine nucleotide-binding protein (G protein)-coupled receptors are important in mediating the coupling of the receptors to G proteins. Because the primary sequence of this region is not conserved among all receptors that couple to the same G protein, it has been suggested that some other physicochemical property of this domain may determine G protein activation. To determine the relative contributions of charge distribution and amino acid side chain interactions within this domain of the beta-adrenergic receptor (beta AR) to the activation of the G protein Gs, point mutations were introduced into this region of the beta AR. Replacement of all four of the basic amino acid residues within this region (amino acids 222-236) with serine residues had a negligible effect on the ability of the beta AR to activate Gs. In contrast, replacement of the hydrophobic amino acids within this same region with leucine residues resulted in a mutant receptor that was poorly coupled to Gs. These results suggest that specific hydrophobic interactions within this region of the receptor may play a more significant role than ionic or hydrophilic interactions in mediating G protein activation.