Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 574.5 [Unassigned]
• Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2015
• Mô tả vật lý: Size: p. 522-531 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 261146
• Chủ đề: 1. 59 basic biological sciences; 2. 60 applied life sciences; 3. Computational biology and bioinformatics; 4. Immunology; 5. Viral membrane fusion; 6. X-ray crystallography

Tóm tắt

As the sole viral antigen on the HIV-1?virion surface, trimeric Env is a focus of vaccine efforts. In this paper, 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. Finally, antigenicity-guided structural design can thus be used both to delineate mechanism and to fix conformation, with DS-Env trimers in virus-like-particle and soluble formats providing a new generation of vaccine antigens.