Determining native-like membrane protein structures from cell membrane-derived vesicles.

Dr. Chen Zhao is an assistant professor of Biochemistry and Molecular Biology at the University of Florida.

Transmembrane proteins comprise ~30% of the human proteome and play vital roles in establishing membrane potential, transporting solutes, and signal transduction. Historically, structural studies of these membrane proteins require their extraction from their native cell membrane environment using dispersive reagents such as detergents. While this extraction-based method has been remarkably effective and unveiled numerous membrane protein structures, several limitations call for improvement in membrane protein structural biology methods. Firstly, the physiochemical property of the dispersive agents used for stabilizing membrane protein structures greatly differs from that of the native lipid bilayer membrane, leading to limited correlation between atomic structures and physiology. In addition, these dispersive agents strip away weakly bound lipid and protein molecules, precluding molecular interactions that would normally occur in cells. In response to these challenges, we introduce a method to determine high-resolution transmembrane protein structures directly from native cell membrane vesicles using single particle cryo-electron microscopy (cryo-EM), without the need to remove them from the membrane environment using dispersive reagents. Using the ion channel Slo1 as an example, we discovered several novel structural features in the cell membrane environment, such as new lipid and ion binding sites that are otherwise unresolved in detergent-based structures. We believe our method presents an exciting future direction for the structural characterization of transmembrane proteins.

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Hosted by Dr. Marcel Goldschen-Ohm

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