Figure 1.

Identification of an evolutionarily conserved mechanism of G protein activation by proteins with a GBA motif.A, timeline of some discoveries related to non-GPCR regulators of G proteins. Nonreceptor GEFs were identified and characterized later than GAPs and GDIs. B, GIV/Girdin contains and evolutionarily conserved motif required for the activation of G protein signaling. C, alignment of GBA motifs identified in proteins and of GBA-like peptides. D, GBA motif in evolution. CCDC88 proteins acquired a GBA motif upon gene duplication in the transition from invertebrates to vertebrates, whereas the GBA motif–containing protein GBAS-1 appeared earlier by convergent evolution from a distinct lineage in nematodes. GBA, Gα-binding-and-activating; GEF, guanine-nucleotide exchange factor; GIV, Gα-interacting vesicle-associated protein; GPCR, G protein–coupled receptor.