GPRGoLoco Motifs

Recently, a diverse group of proteins containing 25-30 residue GPR (G-protein regulatory) [53,54], or GoLoco [55]

Figure 6 The complex of Gp^Gpj is colored yellow, except for the second (from the N-terminus) WD repeat, which is rendered in orange. The four-stranded antiparallel p "blades" that comprise the propeller fold are numbered. Individual strands in one repeat are lettered (a) through (d), in order of sequence. The Gy subunit is green. The amino termini of both sub-units are labeled.

motifs were shown to inhibit, like GPy, the dissociation of GDP from Ga;i and Gao. GPR/GoLoco motifs bind only to the GDP-bound Ga isoforms and also inhibit binding of GyP [53,56,57]. The GPR/GoLoco repeat from RGS14 adopts an extended conformation when bound to Ga;i.GDP, forming contacts with Switch II and crossing the gap between the Ras-like and helical domains. A conserved arginine residue from GoLoco engages the GDP P-phosphate, thus stabilizing the nucleotide within the catalytic site. GPR-containing molecules provide a mechanism for receptor-independent activation of GPy signaling pathways, while inhibiting reactivation of Gai1.

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