Biophysical characterisation of SMALPs

Biochem Soc Trans. 2021 Oct 13:BST20201088. doi: 10.1042/BST20201088. Online ahead of print.ABSTRACTMembrane proteins such as receptors, ion channels and transport proteins are important drug targets. The structure-based study of membrane proteins is challenging, especially when the target protein contains both soluble and insoluble domains. Most membrane proteins are insoluble in aqueous solvent and embedded in the plasma membrane lipid bilayer, which significantly complicates biophysical studies. Poly(styrene-co-maleic acid) (SMA) and other polymer derivatives are increasingly common solubilisation agents, used to isolate membrane proteins stabilised in their native lipid environment in the total absence of detergent. Since the initial report of SMA-mediated solubilisation, and the formation of SMA lipid particles (SMALPs), this technique can directly isolate therapeutic targets from biological membranes, including G-protein coupled receptors (GPCRs). SMA now allows biophysical and structural analyses of membrane proteins in solution that was not previously possible. Here, we critically review several existing biophysical techniques compatible with SMALPs, with a focus on hydrodynamic analysis, microcalorimetric analysis and optical spectroscopic techniques.PMID:34643233 | DOI:10.1042/BST20201088

Source: Biochemical Society Transactions - October 13, 2021 Category: Biochemistry Authors: Stephanie A Nestorow Tim R Dafforn Verna Frasca Source Type: research