Structure and Activity of Lipid Bilayer Within a Membrane-Protein Transporter
Structure and activity of lipid bilayer within a membrane-protein transporter Weihua Qiua,b,1, Ziao Fuc,1, Guoyan G. Xua, Robert A. Grassuccid, Yan Zhanga, Joachim Frankd,e,2, Wayne A. Hendricksond,f,g,2, and Youzhong Guoa,b,2 aDepartment of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA 23298; bInstitute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, VA 23219; cIntegrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University, New York, NY 10032; dDepartment of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032; eDepartment of Biological Sciences, Columbia University, New York, NY 10027; fDepartment of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032; and gNew York Structural Biology Center, New York, NY 10027 Contributed by Wayne A. Hendrickson, October 15, 2018 (sent for review July 20, 2018; reviewed by Yifan Cheng and Michael C. Wiener) Membrane proteins function in native cell membranes, but extrac- 1.9 Å (30). Nevertheless, the mechanism of active transport is still tion into isolated particles is needed for many biochemical and far from clear, in part because crucial structural information re- structural analyses. Commonly used detergent-extraction meth- garding protein–lipid interaction is missing (31). The AcrB trimer ods destroy naturally associated lipid bilayers. Here, we devised a has a central cavity between transmembrane (TM) domains of the detergent-free method for preparing cell-membrane nanopar- three protomers, where a portion of lipid bilayer may exist (26). ticles to study the multidrug exporter AcrB, by cryo-EM at 3.2-Å Although detergent molecules and some alkane chains have been resolution.
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