The Galpha protein Gpa2 controls yeast differentiation by interacting with kelch repeat proteins that mimic Gbeta subunits.

G protein coupled receptors (GPCR) sense diverse ligands and signal via heterotrimeric G proteins. The Saccharomyces cerevisiae GPCR Gpr1 senses glucose and controls filamentous growth via an unusual Galpha protein, Gpa2, which lacks any known Gbetagamma subunits. Our genetic and biochemical studies identify Gpa2 interaction partners (Gpb1/2, Gpg1) and provide evidence that these proteins function as G protein subunit mimics and signaling effectors. Gpb1 and Gpb2 lack the seven WD-40 repeats found in Gbeta subunits and instead contain seven kelch repeats implicated in protein-protein interactions. Gbeta subunits and the kelch repeat protein galactose oxidase fold into strikingly similar seven-bladed beta propellers. Our studies demonstrate that Gpa2 signals in conjunction with Gbeta structural mimics and that homologous G protein subunits or effectors may be conserved in multicellular eukaryotes.