Different α-adrenergic receptor sequences required for activating different Gα subunits of Gq class of G proteins

Abstract

In order to understand the specific interactions between receptors and guanine nucleotide-binding regulatory protein (G proteins), we attempted to delineate the α1B-adrenergic receptor sequences involved in activation of the α 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 Ga subunits of the Gq class. Our results indicate that the receptor sequences required for activating Gaq/11, Gα14, or Gα16 are different. The sequence extending from residues Lys240 to His252 is required for activation of Gαq/11, but not for activation of Gα14 or Gα16. Two segments in the third loop of the receptor are required for activation of Gα14: 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 Gα14 coupling, but not for Gα16 or Gαq/11 coupling. Furthermore, the three amino acids stretch (Tyr217 to Val219) included in the N-terminal segment is not only required for Gα14 coupling, but also for Gαq/11 coupling. It may be involved to some extent in Gα16 coupling as well.