Identification of a region in G protein gamma subunits conserved across species but hypervariable among subunit isoforms

The heterotrimeric GTP binding proteins, G proteins, consist of three disti nct subunits: alpha, beta, and gamma. There are 12 known mammalian gamma su bunit genes whose products are the smallest and most variable of the G prot ein subunits. Sequencing of the bovine brain gamma (10) protein by electros pray mass spectrometry revealed that it differs from the human protein by a n Ala to Val substitution near the N-terminus. Comparison of gamma isoform subunit sequences indicated that they vary substantially more at the N-term inus than at other parts of the protein. Thus, species variation of this re gion might reflect the lack of conservation of a functionally unimportant p art of the protein. Analysis of 38 gamma subunit sequences from four differ ent species shows that the N-terminus of a given gamma subunit isoform, is as conserved between different species as any other part of the protein, in cluding highly conserved regions. These data suggest that the N-terminus of gamma is a functionally important part of the protein exhibiting substanti al isoform-specific variation.