A novel G protein alpha subunit containing atypical guanine nucleotide-binding domains is differentially expressed in a molluscan nervous system

Publication Type:

Journal Article


J Biol Chem, Volume 270, Number 32, p.18804-18808 (1995)

DOI Name (links to online publication)



Amino Acid Sequence; Animals; Base Sequence; Binding Sites; Brain; Central Nervous System; chemistry; Cholera Toxin; Dna; DNA; Complementary; genetics; Glutamic Acid; GTP-Binding Proteins; Guanine Nucleotides; In Situ Hybridization; isolation; &; purific


We described the characterization of a novel G protein alpha subunit, G alpha a. cDNA encoding this subunit was cloned from the central nervous system of the mollusc Lymnaea stagnalis. The deduced protein contains all characteristic guanine nucleotide-binding domains of G alpha subunits but shares only a limited degree of overall sequence identity with known subtypes (approximately 30%). Moreover, two of the nucleotide-binding domains exhibit salient deviations from corresponding sequences in other G protein alpha subunits. The A domain, determining kinetic features of the GTPase cycle, contains a markedly unique amino acid sequence (ILIIGGPGAGK). In addition, the C domain is also clearly distinct (DVAGQRSL). The presence of a leucine in this motif, instead of glutamic acid, has important implications for hypotheses concerning the GTPase mechanism. In contrast to other G alpha subtypes, G alpha a has no appropriate N-terminal residues that could be acylated. It does contain the strictly conserved arginine residue that serves as a cholera toxin substrate in G alpha s and G alpha t but lacks a site for ADP-ribosylation by pertussis toxin. In situ hybridization experiments indicate that G alpha a-encoding mRNA is expressed in a limited subpopulation of neurons within the Lymnaea brain. These data suggest that G alpha a defines a separate class of G proteins with cell type-specific functions