Biological Insights from SMA-extracted Proteins

Alice Rothnie*, Lucas Unger, Alejandro Ronco-Campaña, Philip Kitchen, Roslyn Bill

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


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.
Original languageEnglish
Pages (from-to)1349-1359
Number of pages11
JournalBiochemical Society Transactions
Issue number3
Early online date10 Jun 2021
Publication statusPublished - Jun 2021

Bibliographical note

© 2021 The Author(s)
This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY). Open access for this article was enabled by the participation of Aston University in an all-inclusive Read & Publish pilot with Portland Press and the Biochemical Society under a transformative agreement with JISC.

Funding: We are grateful for funding from the European Union's Horizon 2020 research and innovation programme under Marie Sklodowska Curie grant agreement No. 847,419 (MemTrain; through a studentship to L.U. and A.R-C.) and from Aston University (through a 50th Anniversary Prize Fellowship to P.K.)


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