HIV-1 Env trimer opens through an asymmetric intermediate in which individual protomers adopt distinct conformations
- Yale University School of Medicine, United States
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States
- Weill Cornell Medical College of Cornell University, United States
- Tufts University School of Medicine, United States
Abstract
HIV-1 entry into cells requires binding of the viral envelope glycoprotein (Env) to receptor CD4 and coreceptor. Imaging of individual Env molecules on native virions shows Env trimers to be dynamic, spontaneously transitioning between three distinct well-populated conformational states: a pre-triggered Env (State 1), a default intermediate (State 2) and a three-CD4-bound conformation (State 3), which can be stabilized by binding of CD4 and coreceptor-surrogate antibody 17b. Here, using single-molecule Fluorescence Resonance Energy Transfer (smFRET), we show the default intermediate configuration to be asymmetric, with individual protomers adopting distinct conformations. During entry, this asymmetric intermediate forms when a single CD4 molecule engages the trimer. The trimer can then transition to State 3 by binding additional CD4 molecules and coreceptor.
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Author details
Funding
National Institutes of Health (GM116654)
- Walther Mothes
National Institutes of Health (AI116262)
- James B Munro
National Institutes of Health (GM098859)
- Scott C Blanchard
National Institutes of Health (GM056550)
- Scott C Blanchard
- Walther Mothes
Cancer Research Institute (Irvington Fellows Program)
- James B Munro
National Institutes of Health (AI042853)
- James B Munro
China Scholarship Council (Yale World Scholars)
- Xiaochu Ma
National Institutes of Health (GM103310)
- Peter D Kwong
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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HIV-1 Env trimer opens through an asymmetric intermediate in which individual protomers adopt distinct conformations
eLife 7:e34271.
https://doi.org/10.7554/eLife.34271
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