Fast Magic Angle Spinning for Protein Solid-State NMR Spectroscopy

Abstract

High-resolution magic-angle spinning (MAS) solid-state NMR spectroscopy has recently emerged as a very promising structural biology tool for insoluble proteins such as fibrils and membrane proteins. This collectively resulted from technological and methodological advances in several areas such as high-field magnets, decoupling, and recoupling techniques, isotope labeling methods, and MAS probe technology. In particular, the introduction of fast (>40 kHz) and ultrafast (>60 kHz) MAS probes has prompted the development of several high-sensitivity experimental methods. For paramagnetic samples, a much shorter recycle time may be used for faster data acquisition since satisfactory resolution is achievable without high-power decoupling under fast-MAS condition. More generally, proton detection methods have been developed on the basis of fast MAS, enhancing detection sensitivity by an order of magnitude. These methods have generated profound impact on several previously sensitivity-challenged applications such as surface-bound species, drugs and other organic molecules, and peptide/protein pharmaceuticals without isotope enrichment. Furthermore, they have paved the way to study large uniformly labeled proteins in the solid state. Keywords: solid-state NMR; fast magic-angle spinning; proton detection; sensitivity; resolution; chemical shift assignments; structure determination; paramagnetic doping; pharmaceutical analysis