Applications of Multidimensional Solid-State NMR Spectroscopy to Membrane Proteins

Abstract

A singular challenge in structural biology is the experimental determination of the structures of membrane proteins. Because these proteins are difficult to crystallize there are few examples with structures determined by X-ray diffraction (Deisenhofer et al., 1985; Weiss et al. 1991; Iwata et al., 1995). Multidimensional solution NMR methods are difficult to apply to membrane proteins because of the slow reorientation rates and broad resonance linewidths that accompany solubilisation in detergent micelles. Proteins in the other well characterized model membrane environment of lipid bilayers are even less well suited for solution NMR methods because the individual protein molecules are effectively immobilized when complexed with phospholipids. However, it is useful to keep in mind that NMR studies of membrane proteins are formidable because of the motional properties of the samples rather than any intrinsic properties of the proteins themselves and that solid state NMR spectroscopy is fully capable of overcoming the difficulties resulting from the very slow reorientation rates (Opella, 1994).