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
