作者
Young Do Kwon, Marie Pancera, Priyamvada Acharya, Ivelin S Georgiev, Emma T Crooks, Jason Gorman, M Gordon Joyce, Miklos Guttman, Xiaochu Ma, Sandeep Narpala, Cinque Soto, Daniel S Terry, Yongping Yang, Tongqing Zhou, Goran Ahlsen, Robert T Bailer, Michael Chambers, Gwo-Yu Chuang, Nicole A Doria-Rose, Aliaksandr Druz, Mark A Hallen, Adam Harned, Tatsiana Kirys, Mark K Louder, Sijy O'dell, Gilad Ofek, Keiko Osawa, Madhu Prabhakaran, Mallika Sastry, Guillaume BE Stewart-Jones, Jonathan Stuckey, Paul V Thomas, Tishina Tittley, Constance Williams, Baoshan Zhang, Hong Zhao, Zhou Zhou, Bruce R Donald, Lawrence K Lee, Susan Zolla-Pazner, Ulrich Baxa, Arne Schön, Ernesto Freire, Lawrence Shapiro, Kelly K Lee, James Arthos, James B Munro, Scott C Blanchard, Walther Mothes, James M Binley, Adrian B McDermott, John R Mascola, Peter D Kwong
发表日期
2015/7
期刊
Nature structural & molecular biology
卷号
22
期号
7
页码范围
522-531
出版商
Nature Publishing Group US
简介
As the sole viral antigen on the HIV-1–virion surface, trimeric Env is a focus of vaccine efforts. Here we present the structure of the ligand-free HIV-1–Env trimer, fix its conformation and determine its receptor interactions. Epitope analyses revealed trimeric ligand-free Env to be structurally compatible with broadly neutralizing antibodies but not poorly neutralizing ones. We coupled these compatibility considerations with binding antigenicity to engineer conformationally fixed Envs, including a 201C 433C (DS) variant specifically recognized by broadly neutralizing antibodies. DS-Env retained nanomolar affinity for the CD4 receptor, with which it formed an asymmetric intermediate: a closed trimer bound by a single CD4 without the typical antigenic hallmarks of CD4 induction. Antigenicity-guided structural design can thus be used both to delineate mechanism and to fix conformation, with DS-Env trimers in virus-like …
学术搜索中的文章
Y Do Kwon, M Pancera, P Acharya, IS Georgiev… - Nature structural & molecular biology, 2015