Lipid Dynamics and Protein-Lipid Interactions in Integral Membrane Proteins: Insights from Solid-State NMR

Abstract

Integral membrane proteins are of great biomedical and biological interest but are challenging targets for structural biology. One of the challenges is the characterization of membrane protein interactions with a proper lipid bilayer that mimics their native environment. The membrane environment can directly affect the structure of integral membrane proteins and can also be crucial for optimal activity. Solid-state NMR is in a unique position to probe the protein–lipid interplay, by providing insight into both structure and dynamics of the protein as well as the lipids. Under native conditions, biological membranes are characterized by a dynamic and disordered ‘liquid crystalline’ structure. Solid-state NMR experiments are affected by dynamics, at times in negative ways, but the dynamics can also be leveraged to gain valuable information, including orientational constraints. This article discusses approaches to probe integral membrane protein interactions with lipids, and the role of lipid dynamics, through the use of static as well as magic-angle-spinning solid-state NMR. Keywords: solid-state NMR; membrane proteins; molecular dynamics; protein structure; order parameters; relaxation; oriented samples; magic-angle-spinning NMR