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Title: Single Particle Cryo-EM of Membrane Proteins in Lipid Nanodisc
Originating Office: IAS
Speaker: Cheng, Yifan
Issue Date: 26-Sep-2017
Event Date: 26-Sep-2017
Group/Series/Folder: Record Group 8.15 - Institute for Advanced Study
Series 3 - Audio-visual Materials
Location: 8.15:3 EF
Notes: Title from slide title: Single particle cryo-EM: a revolution in structural biology.
IAS distinguished lecture.
Co-sponsored by Center of Systems Biology and Human Health.
Title from opening screen.
Abstract: In the last few years, major technological breakthroughs, particularly the development of new direct electron detection cameras and associated technologies, have enabled single particle cryo-electron microscopy (cryo-EM) to become the technique of choice for high-resolution structure determination of many challenging biological macromolecules. Atomic structures of many membrane proteins, particularly ion channels, that are refractory to crystallization have now determined by this method, including the speaker's previous work of determining the atomic structures of TRPV1 and TRPA1. In most of these studies, membrane proteins were solubilized in detergent, or detergent-like amphipathic polymers ('amphipols'), with a few exceptions. However, for many ion channels and integral membrane proteins in general, maintaining purified proteins in a near-native lipid bilayer environment is crucial for visualizing specific and functionally important lipid-protein interactions, and more importantly, for maintaining protein functionality. The next technical challenge for single particle cryo-EM studies of membrane proteins is, therefore, to enable atomic structure determination of integral membrane proteins in a native or native-like lipid bilayer environment. Lipid nanodisc technology uses membrane-scaffolding proteins (MSP) to reconstitute integral membrane proteins into lipid nanoparticles. This highly native-like system is the first choice for a general platform for single particle cryo-EM of membrane proteins. Recently, the speaker tested the feasibility of using lipid nanodisc in atomic structure determination of relatively small integral membrane proteins, such as TRPV1. He reconstituted TRPV1 ion channel in lipid nanodiscs, and determined atomic structures of nanodisc-embedded TRPV1 in three different conformations. These structures revealed locations of some annular and regulatory lipids that form specific interactions with the channel. Such specific phospholipid interactions enhance binding of a spider toxin to TRPV1 through formation of a tripartite complex. These structures also reveal that, in the absence of vanilloid agonist, a phosphatidylinositol lipid occupies the capsaicin-binding site of TRPV1, providing important clues about physiological mechanisms of channel regulation.
Prof Yifan Cheng received his PhD in physics from Institute of Physics (IP) of Chinese Academy of Sciences in 1991. He furthered his career as a Postdoctoral fellow in IP in 1993 and the Florida State University in 1996-97. In 2006, Prof Cheng joined the University of California at San Francisco and is currently the Professor of Biochemistry and Biophysics. He was also appointed an Investigator of Howard Hughes Medical Institute in 2015.
Prof Cheng’s research focuses on structures and functions of various biological macromolecules; integral membrane proteins and large dynamic macromolecular machineries; and development of enabling technologies to facilitate structural studies of these challenging macromolecules by cryo-EM.
Prof Cheng has been recognized for his scholarly contribution by a number of honors, including the K.H. Kuo Award for Distinguished Scientist by University of California at San Francisco (2014) and the Alexander von Humboldt Foundation Fellowship (1994).
Duration: 84 min.
Appears in Series:8.15:3 - Audio-visual Materials
Videos for Public -- Distinguished Lectures