Advances in Membrane Mimetic Systems for Manipulation and Analysis of Membrane Proteins: Detergents, Polymers, Lipids and Scaffolds

Abstract

Extracting membrane proteins from the hydrophobic environment of the biological membrane, in a physiologically relevant and stable state, suitable for downstream analysis remains a challenge. The traditional route to membrane protein extraction has been to use detergents and the last 15 years or so have seen a veritable explosion in the development of novel detergents with improved properties, making them more suitable for individual proteins and specific applications. There have also been significant advances in the development of encapsulation of membrane proteins in lipid based nanodiscs, either directly from the native membrane using polymers allowing effective capture of the protein and protein‐associated membrane lipids, or via reconstitution of detergent extracted and purified protein into nanodiscs of defined lipid composition. All of these advances have been successfully applied to the study of membrane proteins via a range of techniques and there have been some spectacular membrane protein structures solved using these new approaches. In addition, the first detailed structural and biophysical analyses of membrane proteins retained within a biological membrane have been reported. Here we summarise and review the recent advances with respect to these new agents and systems for membrane protein extraction, reconstitution and analysis.

Membrane-Driven Dimerization of the Peripheral Membrane Protein KRAS: Implications for Downstream Signaling

“…Several types of lipid-based nanoparticles with different shapes and sizes, such as micelles, bicelles, liposomes, and nanodiscs, have been extensively used to elucidate the structural basis and biochemical properties of membrane-bound proteins in the structural biology field [ 35 , 36 ]. Among these nanoparticles, discoidal nanodiscs have increasingly gained attention because nanodiscs provide native lipid-bilayer membranes and enable the preparation of highly stable, homogeneous protein–lipid samples suitable for structural analyses using cryo-electron microscopy (EM) and nuclear magnetic resonance (NMR) [ 37 , 38 , 39 , 40 ].…”