Use of F-19 NMR to probe protein structure and conformational changes

F-19 NMR has proven to be a powerful technique in the study of protein structure and dynamics because the F-19 nucleus is easily incorporated at specific labeling sites, where it provides a relatively nonperturbing yet sensitive probe with no background signals. Recent applications of F-19 NMR in mapping out structural and functional features of proteins, including the galactose-binding protein, the transmembrane aspartate receptor, the CheY protein, dihydrofolate reductase, elongation factor-Tu, and D-lactose dehydrogenase, illustrate the utility of F-19 NMR in the analysis of protein conformational states even in molecules too large or unstable for full NMR structure determination. These studies rely on the fact that the chemical shift of F-19 is extremely sensitive to changes in the local conformational environment, including van der Waals packing interactions and local electrostatic fields. Additional information is provided by solvent-induced isotope shifts or line broadening of the F-19 resonance by aqueous and membrane-bound paramagnetic probes, which may reveal the proximity of a F-19 label to bulk solvent or a biological membrane. Finally, the effect of exchanging conformations on the F-19 resonance can directly determine the kinetic parameters of the conformational transition.