Different alpha 1-adrenergic receptor sequences required for activating different G alpha subunits of Gq class of G...

In order to understand the specific interactions between receptors and guanine nucleotide-binding regulatory protein (G proteins), we attempted to delineate the alpha 1 B-adrenergic receptor sequences involved in activation of the alpha subunits of the Gq class of G proteins. A number of specific mutations were introduced into the third inner loop of the receptor, and the mutants were tested for their abilities to activate different G alpha subunits of the Gq class. Our results indicate that the receptor sequences required for activating G alpha q/11, G alpha 14, or G alpha 16 are different. The sequence extending from residues Lys240 to His252 is required for activation of G alpha q/11, but not for activation of G alpha 14 or G alpha 16. Two segments in the third loop of the receptor are required for activation of G alpha 14: one is located at the N terminus of the loop ending at residue Asn226, and the other is located at the C terminus of the loop starting from residue Ser278. The latter contains a BBXXB motif, which is apparently critical for G alpha 14 coupling, but not for G alpha 16 or G alpha q/11 coupling. Furthermore, the three amino acids stretch (Tyr217 to Val219) included in the N-terminal segment is not only required for G alpha 14 coupling, but also for G alpha q/11 coupling. It may be involved to some extent in G alpha 16 coupling as well.