NMR Structural Studies of Membrane Proteins in Lipid Micelles and Lipid Bilayers

Abstract

Integral membrane proteins regulate major cellular processes in health and disease, including transport, signaling, secretion, adhesion, pathogenesis, and apoptosis, and therefore, represent important targets for structural and functional characterization. Membrane protein structures and functions are regulated by their physical interactions with the surrounding lipids, and NMR is unique in its ability to provide high-resolution information in lipid environments that closely resemble the cellular membranes. Solid-state NMR experiments with proteins in oriented bilayers, and solution NMR experiments with proteins in weakly oriented micelles, provide high-resolution orientation-dependent restraints, which can be combined for protein structure determination and refinement. As previously observed for helical membrane proteins, the NMR spectra of outer membrane barrels in lipid bilayers exhibit characteristic patterns that reflect both protein structure and intra-membrane orientation. Results are presented for mammalian and bacterial α-helical and β-stranded membrane proteins. The NMR structures characterized in lipids provide insights to their distinct functions. (This research was supported by the National Institutes of Health.)