期刊
CELL REPORTS
卷 31, 期 4, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2020.107583
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资金
- NIH Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases [UM1AI100663, UM1 AI144462, R01 AI143563]
- Bill and Melinda Gates Foundation through the Collaboration for AIDS Vaccine Discovery (CAVD) [OPP1115782]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZIAAI005023] Funding Source: NIH RePORTER
Structural and functional studies of HIV envelope glycoprotein (Env) as a transmembrane protein have long been complicated by challenges associated with inherent flexibility of the molecule and the membraneembedded hydrophobic regions. Here, we present approaches for incorporating full-length, wild-type HIV1 Env, as well as C-terminally truncated and stabilized versions, into lipid assemblies, providing a modular platform for Env structural studies by single particle electron microscopy. We reconstitute a full-length Env clone into a nanodisc, complex it with a membrane-proximal external region (MPER) targeting antibody 10E8, and structurally define the full quaternary epitope of 10E8 consisting of lipid, MPER, and ectodomain contacts. By aligning this and other Env-MPER antibody complex reconstructions with the lipid bilayer, we observe evidence of Env tilting as part of the neutralization mechanism for MPER-targeting antibodies. We also adapt the platform toward vaccine design purposes by introducing stabilizing mutations that allow purification of unliganded Env with a peptidisc scaffold.
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