One-third of eukaryotic proteins are integrated within membranes, as are the targets of 40% of approved drugs. However, the lack of a general means of solubilizing, stabilizing and structurally characterizing these active membrane proteins has frustrated efforts to understand their mechanisms and exploit their potential value.

However, using nanoparticles, scientists from the Universities of Birmingham and Warwick have developed a technique to preserve membrane proteins intact, enabling detailed analysis of their structure and molecular functions. These new findings will give scientists access to previously ignored proteins deemed too unstable to work with.

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."

As published online in the Journal of the American Chemical Society, the researchers report that bilayer disks formed by phospholipids and styrene maleic anhydride copolymer preserve the functional and structural integrity of α-helical and β-barrel transmembrane proteins. They form 11 nm particles that are monodispersed, biocompatible, thermostable, and water-soluble, allowing diverse membrane proteins to be simply and rapidly presented for virtually any in vitro analysis.

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."

Read the paper here: http://pubs.acs.org/doi/abs/10.1021/ja810046q