Choosing membrane mimetics for NMR structural studies of transmembrane proteins

Abstract

The native environment of membrane proteins is complex and scientists have felt the need to simplify it to reduce the number of varying parameters. However, experimental problems can also arise from oversimplification which contributes to why membrane proteins are under-represented in the protein structure databank and why they were difficult to study by nuclear magnetic resonance (NMR) spectroscopy. Technological progress now allows dealing with more complex models and, in the context of NMR studies, an incredibly large number of membrane mimetics options are available. This review provides a guide to the selection of the appropriate model membrane system for membrane protein study by NMR, depending on the protein and on the type of information that is looked for. Beside bilayers (of various shapes, sizes and lamellarity), bicelles (aligned or isotropic) and detergent micelles, this review will also describe the most recent membrane mimetics such as amphipols, nanodiscs and reverse micelles. Solution and solid-state NMR will be covered as well as more exotic techniques such as DNP and MAOSS.

The X-ray Structure of NccX from Cupriavidus metallidurans 31A Illustrates Potential Dangers of Detergent Solubilization When Generating and Interpreting Crystal Structures of Membrane Proteins

“…DPC, n-dodecyl ␤-D-maltopyranoside, n-octyl ␤-D-glucopyranoside, or tetraethylene glycol monooctyl ether (C 8 E 4 )), but only DPC allowed achieving both purification and crystallization. Although widely used in membrane protein investigation (41,42), DPC has been seldom used for crystallization, although DPC micelles can be considered a membrane mimetic of choice for NMR studies because of the number of structures observed (41). Very recently, the effect of DPC on protein conformation was illustrated in two instances where solution structures obtained in DPC micelles and crystal structuresobtainedeitherin3-lauramidopropyl-N,N-dimethylamine oxide micelles or lipid meso-phase were significantly different.…”

Structural and Dynamic Insights of the Interaction between Tritrpticin and Micelles: An NMR Study

“…These micelles were chosen based on the proposal by Bozelli et al (17) their use allows mimicking the headgroup composition of biological membranes. PC is one of the major phospholipids in the outer leaflet of mammalian membranes and PG is one of the main phospholipids in the outer leaflet of bacterial membranes (57). The dynamic profile of TRP3 can be determined by relaxation experiments.…”

NMR Spectroscopy for Studying Integrin Antagonists

“…However, transmembrane domains pose a particular challenge for conventional solution NMR due to the large molecular weight of the bilayer required to maintain the protein in the correct conformation. Recent advances in solution NMR, particularly the development of membrane nanodiscs that preserve the authentic structure of the native bilayer, have begun to overcome this limitation and provide detailed, high-resolution structural details on association of transmembrane peptides (Warschawski et al, 2011).…”