Protein structure determination by solid-state NMR.

Membrane proteins are a large, diverse group of proteins, representing about 20-30% of the proteomes of most organisms, serving a multitude of cellular functions and more than 40% of drug targets. Knowledge of a membrane protein structure enables us insight into its function and dynamics, and can be used for further rational drug design. Owing to the intrinsic hydrophobicity, flexibility, and instability of membrane proteins, solid-state NMR may offer an unique opportunity to study membrane protein structure, ligand binding, and activation at atomic resolution in the native membrane environment on a wide ranging time scale. Over the past several years, solid-state NMR has made tremendous progress, showing its capability of determining membrane protein structure, ligand binding, and protein dynamic conformation on a variety of time scales at atomic resolution. In this chapter we will mainly discuss some recent achievements on membrane protein structure determination, ligand conformation and binding, structure changes upon activation, and structure of insoluble fibrous proteins investigated by using magic-angle spinning solid-state NMR from the structural biology point of view. Protein dynamics, sensitivity enhancement, and the possibility of chemical shift-based structure determination in solid-state NMR are also briefly touched upon.