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α2A-adrenergic receptors do not interact with G proteins until the receptor is activated (bar).

BÜNEMANN/EMBO

In recent years, scientists have identified many complexes containing most or all of the components needed to mount a particular signaling cascade. In contrast, Peter Hein, Moritz Bünemann (University of Würzburg, Germany), and colleagues find that a G protein signaling pathway works just as well, if not better, when receptor and G protein start out apart.

Several groups have hypothesized that speed and specificity of the many different G protein–mediated pathways might be achieved by precoupling the G protein and its receptor, via direct or indirect binding. But the new FRET analyses show that the two are not together until the receptor is activated. Interactions thus depend on random collisions between receptor and G protein. “Lateral diffusion in the membrane is fast enough,” says Bünemann.

Kinetic analyses reveal...

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