Phosphorylation is usually assumed to regulate signal transduction by triggering a conformational switch. Volkman et al. show that in the signaling protein NtrC, activation by phosphorylation involves stabilization of a preexisting conformation. Nuclear magnetic resonance measurements of backbone dynamics show that both active and inactive conformations are populated in unphosphorylated NtrC, with the inactive form favored. Phosphorylation shifts the equilibrium far toward the active conformation, so that conformational exchange virtually disappears. Thus, allosteric regulation of single domains may be important in signal transduction. Buck and Rosen provide a Perspective on the data.
M. Buck, M. K. Rosen, Flipping a switch. Science 291, 2329-2330 (2001). [Full Text]