However, using nanoparticles, scientists from the Universities of Birmingham and Warwick have found a way to preserve membrane proteins intact, enabling detailed analysis of their structure and molecular functions.
These new findings, which were developed by scientists funded by the Biotechnology and Biological Sciences Research Council (BBSRC), have just been published online in the Journal of the American Chemical Society and will give scientists access to previously ignored proteins deemed too unstable to work with. This could lead to 30 per cent more proteins being available as potential targets for drug development, opening up exciting possibilities in drug discovery.
Professor Michael Overduin from the University of Birmingham, who led the study, explained: ‘We have shown how a polymer can wrap around and preserve membrane proteins intact in stable nanoparticles. Membrane proteins are the most valuable but technically challenging targets for drug discovery. Finding a gentle solution that preserves their structure and activity, yet is robust enough for experimental interrogation, has eluded scientists for decades, but is now available’.
Using a polymer containing suitable phospholipids (styrene maleic acid lipid particles, or SMALPs), the researchers solubilized a pair of membrane proteins and found that the proteins maintained their folded structure, binding and enzyme activities in the SMALPs. Advantages of SMALPs over traditional ways to solubilize proteins, such as detergents, include enhanced stability, activity and spectral quality of the protein membranes.
Dr Tim Dafforn, who jointly ran the study, said: ‘In the past, studies have concentrated largely on soluble proteins as membrane proteins are so difficult to make. However, the discovery of the SMALPs removes this barrier and opens up access to membrane proteins – this has exciting clinical implications as it may enable drug discovery on receptors that are currently too difficult to produce or to study by current methods’.
The full paper is available on the Journal of the American Chemical Society website: ‘Membrane proteins solubilized intact in lipid containing nanoparticles bounded by styrene maleic acid copolymer’.