CHAPTER 21: A Promising Prognosis for Solid-State NMR of Functional Membrane Protein Complexes

Biological solid-state NMR has shown impressive progress over the past 15 years, from the resonance assignment of small soluble proteins to the structure determination of a ∼35 kDa integral membrane protein in a lipid bilayer. This chapter highlights advances in methodology that are enabling the study of ever larger and more complex systems. These include novel probe designs and sample types that make it possible to apply NMR to more physiological samples, as well as methods for sensitivity enhancement that will make it possible to extend NMR to large proteins and multi-protein complexes in which the concentration of the protein or interface of interest may be quite low. Finally, studies of three membrane protein complexes illustrate the promise of approaches ranging from complete structure determination to targeted measurements for understanding structure and mechanism in such systems. Solid-state NMR is poised to make key contributions to understanding how proteins function in the large complexes they form in cells, which is critical to understanding fundamental biological processes and providing insights of medical importance.