From polymer chemistry to structural biology: The development of SMA and related amphipathic polymers for membrane protein extraction and solubilisation. (July 2019)

• Record Type: Journal Article
• Authors: Bada Juarez, Juan Francisco; Harper, Andrew J.; Judge, Peter J.; Tonge, Stephen R.; Watts, Anthony
• Is Part Of: Chemistry and physics of lipids. Volume 221(2019)
• Page Start: 167
• Page End: 175
• Publication Date: 2019-07
• Subjects: ABC ATP binding cassette -- alt-SMA alternating hydrolysed copolymer of styrene and maleic anhydride -- CTC charge-transfer complex -- DIBMA hydrolysed copolymer of diisobutylene and maleic anhydride -- DMPC 1, 2-dimyristoyl-sn-glycero-3-phosphocholine -- DPPC 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine -- EM electron microscopy -- HDL high-density lipoprotein -- LCP lipidic cubic phase -- MA maleic acid -- MSP membrane scaffold protein -- PEAA poly(2-ethacrylic acid) polymer -- PMA poly(methacrylate) -- SMA hydrolysed copolymer of styrene and maleic anhydride -- SMAnh non-hydrolysed copolymer of styrene and maleic anhydride -- SMA-SH thiol derivative of SMA; Lipodisq -- Lipid nanoparticles -- SMA poylmer -- Amphipathic polymers -- Drug delivery -- Structural biology -- Polymer chemistry -- Membrane protein -- Hypercoiling amphipathic polymers -- Discoidal lipid nanoparticles -- Polymer labelling -- SMALP -- SMA lipid nanoparticles -- Native nanodiscs -- Nanodiscs -- DIBMA; Lipids -- Periodicals; Lipids -- Periodicals; Lipides -- Périodiques; Lipids; Periodicals; Electronic journals; 547.77
• DOI: 10.1016/j.chemphyslip.2019.03.008
• Languages: English
• ISSNs: 0009-3084

Abstract

Highlights: The development of amphiphilic polymers, including SMA, that are able to extract membrane proteins into lipid nanoparticles. Discussion of the chemical behaviour of hypercoiling amphipathic polymers and their response to changes in pH. Comparison of different amphipathic polymers used to form discoidal lipid nanoparticles and their tolerance to metal ions. Recent developments in amphipathic polymer design to expand the applications of lipid nanoparticles for structural biology. Methods for labelling SMA polymers for fluorescence microscopy and in vivo biodistribution studies. Abstract: Nanoparticles assembled with poly(styrene-maleic acid) copolymers, identified in the literature as Lipodisq, SMALPs or Native Nanodisc, are routinely used as membrane mimetics to stabilise protein structures in their native conformation. To date, transmembrane proteins of varying complexity (up to 8 beta strands or 48 alpha helices) and of a range of molecular weights (from 27 kDa up to 500 kDa) have been incorporated into this particle system for structural and functional studies. SMA and related amphipathic polymers have become versatile components of the biochemist's tool kit for the stabilisation, extraction and structural characterization of membrane proteins by techniques including cryo-EM and X-ray crystallography. Lipodisq formation does not require the use of conventional detergents and thus avoids their associated detrimental consequences. Here the development of this technology, from its fundamental concept and design to the diverse range of experimental methodologies to which it can now be applied, will be reviewed.