Abstract
In the twelve years since styrene maleic acid (SMA) was first used to extract and purify a membrane protein within a native lipid bilayer, this technological breakthrough has provided insight into the structural and functional details of protein–lipid interactions. Most recently, advances in cryo-EM have demonstrated that SMA-extracted membrane proteins are a rich-source of structural data. For example, it has been possible to resolve the details of annular lipids and protein–protein interactions within complexes, the nature of lipids within central cavities and binding pockets, regions involved in stabilising multimers, details of terminal residues that would otherwise remain unresolved and the identification of physiologically relevant states. Functionally, SMA extraction has allowed the analysis of membrane proteins that are unstable in detergents, the characterization of an ultrafast component in the kinetics of electron transfer that was not possible in detergent-solubilised samples and quantitative, real-time measurement of binding assays with low concentrations of purified protein. While the use of SMA comes with limitations such as its sensitivity to low pH and divalent cations, its major advantage is maintenance of a protein's lipid bilayer. This has enabled researchers to view and assay proteins in an environment close to their native ones, leading to new structural and mechanistic insights.
Highlights
Membrane proteins carry out a wide range of critical functions and are key targets for drug discovery [1]
styrene maleic acid co-polymers (SMA) inserts into membranes and forms small discs of membrane surrounded by the polymer, termed SMA lipid particles (SMALPs) [11]
Once formed, the SMALPs are stable and do not require buffers to be supplemented with free SMA, unlike detergents where the concentration of detergent must be kept above the critical micelle concentration (CMC) for all downstream processes [15]
Summary
Membrane proteins carry out a wide range of critical functions and are key targets for drug discovery [1]. In 2009 the use of styrene maleic acid co-polymers (SMA) for the effective extraction/solubilisation of membrane proteins was first reported [10]. Membrane proteins extracted within SMALPs retain their natural lipid bilayer environment, yet are small and soluble and amenable to many different downstream techniques [15].
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