Though crucial to life and highly relevant to many diseases, membrane proteins offer fascination and frustration in equal measure to the biochemist. Proteins that have evolved to exist within the complex chemistry of the lipid bilayer rarely prosper when removed from it, yet purification of proteins is a cornerstone of biochemistry. Research in our laboratory focuses on solving this dilemma.
We use an amphipathic copolymer of 2:1 styrene: maleic acid (SMA) that has been shown to directly solubilize most biological membranes, to stabilize membrane proteins, and to be amenable to biophysical, functional and structural analyses. Crucially, SMA solubilizes lipids rather than proteins, forming SMA lipid particles (SMALPs) in which membrane protein are retained in their native lipid environment and exhibit excellent functional and structural stability.
As our understanding of SMA and SMALPs deepens, we have had success in the purification and study of more than 50 membrane proteins with a variety of architectures and sizes, both beta barrels and alpha helical proteins from 40 to 400 kDa in size. Here I present an overview of this work, and show the ongoing method developments that we have pursued to broaden the applications of SMA and SMALPs to membrane protein research.
Naomi completed her undergraduate degree at the University of Oxford, and stayed on to do a PhD studying human ATP-binding cassette (ABC) transporters under the supervision of Richard Callaghan. Her first post-doctoral position at the University of Manchester continued this theme of ABC protein work, with a focus on the structure and function of CFTR. Naomi now works at the University of Birmingham developing a novel method for membrane protein purification using amphipathic polymers of styrene and maleic acid.