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Involvement of specific hydrophobic, but not hydrophilic, amino acids in the third intracellular loop of the beta-adrenergic receptor in the activation of Gs
Bethesda, MD: American Society for Pharmacology and Experimental Therapeutics
Erscheinungsjahr
1992
Quelle
MEDLINE
Beschreibungen/Notizen
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.