Membrane protein structure: the contribution and potential of novel solid state NMR approaches.

Alternative methods for describing molecular detail for large integral membrane proteins are required in the absence of routine crystallographic approaches. Novel solid state NMR methods, devised for the study of large molecular assemblies, are now finding applications in biological systems, including integral membrane proteins. Wild-type and genetically engineered proteins can be investigated and detailed information about side chains, prosthetic groups, ligands (e.g. drugs) and binding sites can be deduced. The molecular structure and dynamics of selected parts of the proteins are accessible by a range of different solid state NMR approaches. Inter- and intra-atomic distances can be determined rather accurately (within ångströms) and the orientation of molecular bonds (within 2 degrees) can be measured in ideal cases. Here, a brief description of the methods is given and then some specific examples described with an indication of the future potential for the approaches in studying membrane proteins. It is anticipated that this emerging NMR methodology will be more widely used in the future, not only for resolving local structure, but also for more expansive descriptions of membrane protein structure at atomic resolution.