Yuan Gao is a fifth-year graduate student in the Biophysics PhD program at the University of California, San Francisco. He is a joint student between the research groups of Dr. David Julius and Dr. Yifan Cheng, focusing on structural studies and lipid
modulation of TRP ion channels. Mr. Gao and his colleagues recently demonstrated the potential of combining single particle cryo-EM with lipid nanodisc technology to obtain atomic-resolution structures of integral membrane proteins in a close-to-native
environment. The study was published in Nature last year and has generated great enthusiasm among researchers in the EM field. Mr. Gao was invited to present his findings at several conferences, including the Biophysical Society Meeting (2016) and
the 3DEM Gordon Research Conference (2016).
Before joining UCSF, Yuan Gao obtained a bachelor’s degree in Biotechnology and a master’s degree in Biochemistry from Shanghai Jiao Tong University in Shanghai, China.
When integral membrane proteins are visualized in detergents or other artificial systems, an important layer of information is lost regarding lipid interactions and their effects on protein structure. This is especially relevant to proteins for which
lipids play both structural and regulatory roles. Here, we demonstrate the power of combining electron cryo-microscopy with lipid nanodisc technology to ascertain the structure of an integral membrane protein, the TRPV1 ion channel, in a native bilayer
environment. Using this approach, we could ascertain the locations of annular and regulatory lipids, enabling us to show that specific phospholipid interactions enhance binding of a spider toxin to TRPV1 through formation of a tripartite complex.
Furthermore, phosphatidylinositol lipids occupy the binding site for capsaicin and other vanilloid ligands, suggesting a mechanism whereby chemical or thermal stimuli elicit channel activation by promoting release of bioactive lipids from a critical
allosteric regulatory site.