Tripping a switch: PDZRhoGEF rgRGS-bound Galpha13.

Ras superfamily guanine nucleotide-binding proteins, such as G-proteins and small GTPases, are a paradigm for two-state molecular switches in cell signaling. Recent experimental and theoretical studies question this simple model. Now Chen et al. (2008) provide evidence that the rgRGS domain of PDZRhoGEF has evolved to “trip” the nucleotide-dependent switch of the subunit of the heterotrimeric G-protein, Gα13, so that it can also bind to its GDP state.