Abstract
The elucidation of the structures and interactions of proteins and lipids in intact biological membranes remains largely uncharted territory. However, this information is crucial for understanding how organelles are assembled and how transmembrane machines transduce signals. The challenge of seeing how lipids and proteins engage each other in vivo remains difficult but is being aided by a group of amphipathic copolymers that spontaneously fragment native membranes into native nanodiscs. Poly(styrene-co-maleic acid) (SMA) copolymers have proven adept at converting membranes, cells and tissues directly into SMA lipid particles (SMALPs), allowing endogenous lipid: protein complexes to be prepared and analyzed. Unlike other amphipathic polymers such as amphipols, SMALP formation requires no conventional detergents, which typically strip lipid molecules from proteins and can destabilize multimers. A collaborative community of hundreds of investigators known as the SMALP network has emerged to develop and apply new technologies and identify new challenges and design potential solutions. In this contribution, we review recent practices and progress, focusing on novel SMA copolymers, modifications, alternatives and mechanisms. In addition, a brief overview will be provided, with reference to the further contributions to this special issue on the SMALP technology.
Highlights
Lipid molecules are bound to the surfaces of all membrane proteins, and have profound influences on their structures, stabilities and activities
poly(styrene-co-maleic acid) (SMA) copolymers bind to biological membranes through the hydrophobic insertion of the styrene groups into the lipid bilayer where they pack against the acyl tails while preserving protein activity and stability [1]
styrene maleic acid lipid particle (SMALP) include the protein-bound lipids, which are preserved by the styrene groups that pack against their lipid acyl chains [11,12]
Summary
Lipid molecules are bound to the surfaces of all membrane proteins, and have profound influences on their structures, stabilities and activities. Once removed by classical ‘head and tail’ detergents, the biological lipid ligands are essentially impossible to replace as originally bound This realization led to testing and optimization of the use of amphipathic copolymers for isolation of detergent-free, biologically intact lipid:protein complexes by a research group at the University of Birmingham, UK, starting in 2005. This effort resulted in the report in 2009 that SMA copolymers are able to spontaneously convert membranes into native nanodiscs, as demonstrated with palmitoyl transferase PagP and bacteriorhodopsin proton pump, which retain their respective structure and activity in SMALPs [1]. Shown far to be capable of this unique activity are the specific focus here
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