ArticleProceedings of the National Academy of Sciences of the United States of America2015
Kinetically coupled folding of a single HIV-1 glycoprotein 41 complex in viral membrane fusion and inhibition.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Nanobody-Based Bioconjugates as Potent and Broadly Active Inhibitors of HIV Entry.Journal of the American Chemical Society · 2026Article
- Tracking the protein conformational motions driving HIV-1 membrane fusion.Scientific reports · 2026Article
- Real-time Exchange of the Lipid-bound Intermediate and Post-fusion States of the HIV-1 gp41 Ectodomain.Journal of molecular biology · 2022Article
- SNARE Zippering Is Suppressed by a Conformational Constraint that Is Removed by v-SNARE Splitting.Cell reports · 2021Article
- P2X1 Selective Antagonists Block HIV-1 Infection through Inhibition of Envelope Conformation-Dependent Fusion.Journal of virology · 2020Article
- Article
- Probing Intermolecular Interactions within the Amyloid β Trimer Using a Tethered Polymer Nanoarray.Bioconjugate chemistry · 2018Article
- Computation of Hemagglutinin Free Energy Difference by the Confinement Method.The journal of physical chemistry. B · 2017Article
- Energetics, kinetics, and pathway of SNARE folding and assembly revealed by optical tweezers.Protein science : a publication of the Protein Society · 2017Review
- Sequential activation of the three protomers in the Moloney murine leukemia virus Env.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Single-Molecule Protein Folding Experiments Using High-Precision Optical Tweezers.Methods in molecular biology (Clifton, N.J.) · 2017Article
- Hidden Markov Modeling with Detailed Balance and Its Application to Single Protein Folding.Biophysical journal · 2016Article
- α-SNAP Enhances SNARE Zippering by Stabilizing the SNARE Four-Helix Bundle.Cell reports · 2016Article
- Structure-Based Derivation of Protein Folding Intermediates and Energies from Optical Tweezers.Biophysical journal · 2016Article
- Peptide triazole inactivators of HIV-1: how do they work and what is their potential?Future medicinal chemistry · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
HIV-1 glycoprotein 41 (gp41) mediates viral entry into host cells by coupling its folding energy to membrane fusion. Gp41 folding is blocked by fusion inhibitors, including the commercial drug T20, to treat HIV/AIDS. However, gp41 folding intermediates, energy, and kinetics are poorly understood. Here, we identified the folding intermediates of a single gp41 trimer-of-hairpins and measured their associated energy and kinetics using high-resolution optical tweezers. We found that folding of gp41 hairpins was energetically independent but kinetically coupled: Each hairpin contributed a folding energy of ∼-23 kBT, but folding of one hairpin successively accelerated the folding rate of the next one by ∼20-fold. Membrane-mimicking micelles slowed down gp41 folding and reduced the stability of the six-helix bundle. However, the stability was restored by cooperative folding of the membrane-proximal external region. Surprisingly, T20 strongly inhibited gp41 folding by actively displacing the C-terminal hairpin strand in a force-dependent manner. The inhibition was abolished by a T20-resistant gp41 mutation. The energetics and kinetics of gp41 folding established by us provides a basis to understand viral membrane fusion, infection, and therapeutic intervention.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.