Fast Magic-Angle Spinning

(19)F NMR spectroscopy is an attractive and growing area of research with broad applications in biochemistry, chemical biology, medicinal chemistry, and materials science. We have explored fast magic angle spinning (MAS) (19)F solid-state NMR in assemblies of HIV-1 capsid protein. Tryptophan residues with fluorine substitutions in the 5 position of the indole ring were used as the reporters. The (19)F chemical shifts for the five tryptophans are distinct, reflecting differences in their local environment. Spin diffusion and radio frequency driven recoupling experiments were performed at MAS frequencies of 35 kHz and 40–60 kHz, respectively. Fast MAS frequencies of 40–60 kHz are essential for consistently establishing (19)F-(19)F correlations, yielding interatomic distances of the order of 20 Å. To our knowledge, this is the first example of (19)F MAS NMR being applied to a very large protein assembly. Our results demonstrate the potential of fast MAS (19)F NMR for structural analysis in large biological assemblies.