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Identification of a novel activator of GOA‐1, a trimeric G protein critical for early stages of C. elegans development
Author(s) -
Coleman Brantley David,
Nguyen Lien Thi,
GarciaMarcos Mikel
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1094.3
Subject(s) - guanine nucleotide exchange factor , g protein coupled receptor , g protein , biology , sequence motif , gtp binding protein regulators , heterotrimeric g protein , gtpase activating protein , 14 3 3 protein , biochemistry , receptor , signal transduction , gene , phosphorylation
Classical activation of trimeric G proteins occurs via guanine nucleotide exchange factor (GEF) activity of GPCRs. However, it has become recently evident that a set of non‐receptor proteins can also activate G proteins. Among these non‐receptor GEFs, GIV is the first one that activates G proteins via a defined motif, i.e., the Gα‐Binding and Activating (GBA) motif. We investigated if a similar GBA motif capable of activating G proteins is present in other unrelated proteins. Our bioinformatics searches revealed a putative GBA sequence in an uncharacterized protein highly expressed in early stages of C. elegans development. Here we demonstrate that this protein, that we call ceGBA, binds directly to GOA‐1, a G protein critical for C. elegans development. By using a combination of site directed‐mutagenesis, homology modeling and biochemistry we demonstrate that ceGBA utilizes its GBA motif to bind to the switch II/α3 helix hydrophobic pocket of inactive GOA‐1 and subsequently activates the G protein by accelerating the rate of nucleotide exchange. These results not only suggest a novel receptor‐independent mechanism of GOA‐1 activation during organismal development but also demonstrate that the GBA motif is a functional module for G protein activation conserved among divergent proteins across evolution.