Fast Magic-Angle Spinning 19F NMR Spectroscopy of HIV-1 Capsid Protein Assemblies

F-19 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) F-19 solid-state NMR spectroscopy in assemblies of HIV-1 capsid protein. Tryptophan residues with fluorine substitution at the 5-position of the indole ring were used as the reporters. The F-19 chemical shifts for the five tryptophan residues 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 F-19-F-19 correlations, yielding interatomic distances of the order of 20 angstrom. Our results demonstrate the potential of fast MAS F-19 NMR spectroscopy for structural analysis in large biological assemblies.