Abstract
The solubilisation of membrane proteins (MPs) necessitates the overlap of two contradictory events; the extraction of MPs from their native lipid membranes and their subsequent stabilisation in aqueous environments. Whilst the current myriad of membrane mimetic systems provide a range of modus operandi, there are no golden rules for selecting the optimal pipeline for solubilisation of a specific MP hence a miscellaneous approach must be employed balancing both solubilisation efficiency and protein stability. In recent years, numerous diverse lipid membrane mimetic systems have been developed, expanding the pool of available solubilisation strategies. This review provides an overview of recent developments in the membrane mimetic field, with particular emphasis placed upon detergents, polymer-based nanodiscs and amphipols, highlighting the latest reagents to enter the toolbox of MP research.
Highlights
Membrane proteins (MPs) are indispensable components of biological membranes contributing enormously to both their diverse functionality and structure
Whilst the assumption of the native 3D structure is inherently determined by the amino acid sequence, a synergistic relationship must be established between membrane-spanning residues and lipids to maintain a stable conformation of the correct oligomeric state
This review aims to provide an overview of the recent innovations in membrane mimetic system innovations, accentuating detergents, polymer-based nanodiscs and amphipols (Figure 1)
Summary
Membrane proteins (MPs) are indispensable components of biological membranes contributing enormously to both their diverse functionality and structure. A significant development in nanodisc technology was the utilisation of the styrene maleic acid (SMA) copolymer to form SMA-lipid particles (SMALPs) in 2009 (Table 1) [55] Such polymer-based nanodiscs display a distinct advantage over their protein stabilised predecessors as they may directly extract proteins from the membrane, negating the need for initial detergent solubilisation, lipids contributing to structure or function likely remain associated with the protein following extraction (Figure 3) [56]. PMA displayed solubilisation efficacy comparable to that of conventional detergents in relatively mild solubilisation conditions (26°C pH 7.4–7.6) with no precipitation in the presence of divalent cations showing clear advantage over SMA [74] Such characteristics imply PMA may yet provide a legitimate membrane mimetic for use in biophysical and high-resolution structural studies. A recent preprint reported the use of CyclAPols in the solubiliation of the model bacterial membrane transporter AcrB which subsequently yielded a 3.2 Å Cryo-EM structure [92]
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