Details

Autor(en) / Beteiligte

• Kwon, Young Do
• Pancera, Marie
• Acharya, Priyamvada
• Georgiev, Ivelin S
• Crooks, Emma T
• Gorman, Jason
• Joyce, M Gordon
• Guttman, Miklos
• Ma, Xiaochu
• Narpala, Sandeep
• Soto, Cinque
• Terry, Daniel S
• Yang, Yongping
• Zhou, Tongqing
• Ahlsen, Goran
• Bailer, Robert T
• Chambers, Michael
• Chuang, Gwo-Yu
• Doria-Rose, Nicole A
• Druz, Aliaksandr
• Hallen, Mark A
• Harned, Adam
• Kirys, Tatsiana
• Louder, Mark K
• O'Dell, Sijy
• Ofek, Gilad
• Osawa, Keiko
• Prabhakaran, Madhu
• Sastry, Mallika
• Stewart-Jones, Guillaume B E
• Stuckey, Jonathan
• Thomas, Paul V
• Tittley, Tishina
• Williams, Constance
• Zhang, Baoshan
• Zhao, Hong
• Zhou, Zhou
• Donald, Bruce R
• Lee, Lawrence K
• Zolla-Pazner, Susan
• Baxa, Ulrich
• Schön, Arne
• Freire, Ernesto
• Shapiro, Lawrence
• Lee, Kelly K
• Arthos, James
• Munro, James B
• Blanchard, Scott C
• Mothes, Walther
• Binley, James M
• McDermott, Adrian B
• Mascola, John R
• Kwong, Peter D

Titel

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

Ist Teil von

• Nature structural & molecular biology, 2015-07, Vol.22 (7), p.522-531

Ort / Verlag

United States

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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-particle and soluble formats providing a new generation of vaccine antigens.