Membrane proteins are essential to signal transduction, nutrient use, and energy exchange between the cell and environment. Many of these proteins are implicated in human diseases (atherosclerosis, Alzheimer's diseases, Parkinson, cancer, and antibiotic resistance) and form excellent targets for drug discovery. Due to difficulty in protein expression, purification, reconstitution into a proper membrane model, and crystallization, however, structural determination of membrane protein has been challenging. This chapter describes recent advances in multidimensional NMR spectroscopy allowing the study of a select set of both peripheral and integral membrane proteins. Surface-binding membrane proteins discussed include amphitropic proteins, antimicrobial LL-37 and anticancer peptides, the HIV-1 gp41 peptides, human α- synuclein and apolipoproteins (A-I, A-II, C-I, C-II, C-III, and E). Also discussed are transmembrane proteins including bacterial outer membrane β-barrel proteins and oligomeric α-helical proteins. In addition, the backbone structure of human chemokine receptor CXCR1, a GPCR with seven transmembrane helices, is available via solid-state NMR studies. These structures are made possible due to reconstruction of membrane proteins in membrane-mimetic constructs such as detergent micelles, bicelles, nanodiscs, and phospholipid bilayers as well as the continued development of modern NMR technologies. In addition to protein dynamics, NMR can be applied to investigation of protein-lipid and protein-ligand interactions. These examples illustrate the unique role solution and solid-state NMR spectroscopy plays in structural biology of membrane proteins.
Keywords: Bicelles, HMQC, membrane proteins, micelles, nanodiscs, NOESY, paramagnetic NMR, protein dynamics, protein-lipid interaction, protein-ligand interaction, protein-protein interaction, RDC, Solid-state NMR, solution NMR, structural biology, TROSY