ArticleProtein science : a publication of the Protein Society2008
Characterization of the steric defense of the HIV-1 gp41 N-trimer region.
Article in Protein science : a publication of the Protein Society, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Investigating the role of a conserved hydrophobic pocket of gp41 in the anti-HIV activity of fusion inhibitors.Protein science : a publication of the Protein Society · 2026Article
- Signal peptide exchange alters HIV-1 envelope antigenicity and immunogenicity.Frontiers in immunology · 2024Article
- Alpaca-derived nanobody targeting the hydrophobic pocket of the HIV-1 gp41 NHR broadly neutralizes HIV-1 by blocking six-helix bundle formation.Current research in microbial sciences · 2024Article
- HIV-1 prehairpin intermediate inhibitors show efficacy independent of neutralization tier.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A variant-proof SARS-CoV-2 vaccine targeting HR1 domain in S2 subunit of spike protein.Cell research · 2022Article
- A Derivative of the D5 Monoclonal Antibody That Targets the gp41 N-Heptad Repeat of HIV-1 with Broad Tier-2-Neutralizing Activity.Journal of virology · 2021Article
- Synergistic Effect by Combining a gp120-Binding Protein and a gp41-Binding Antibody to Inactivate HIV-1 Virions and Inhibit HIV-1 Infection.Molecules (Basel, Switzerland) · 2021Article
- IgG Fc-binding motif-conjugated HIV-1 fusion inhibitor exhibits improved potency and in vivo half-life: Potential application in combination with broad neutralizing antibodies.PLoS pathogens · 2019Article
- A Novel gp41-Binding Adnectin with Potent Anti-HIV Activity Is Highly Synergistic when Linked to a CD4-Binding Adnectin.Journal of virology · 2018Article
- Pharmacokinetic and Chemical Synthesis Optimization of a Potent d-Peptide HIV Entry Inhibitor Suitable for Extended-Release Delivery.Molecular pharmaceutics · 2018Article
- Human Immunodeficiency Virus and Simian Immunodeficiency Virus Maintain High Levels of Infectivity in the Complete Absence of Mucin-Type O-Glycosylation.Journal of virology · 2017Article
- Site-Specific Polymer Attachment to HR2 Peptide Fusion Inhibitors against HIV-1 Decreases Binding Association Rates and Dissociation Rates Rather Than Binding Affinity.Bioconjugate chemistry · 2017Article
- Receptor Activation of HIV-1 Env Leads to Asymmetric Exposure of the gp41 Trimer.PLoS pathogens · 2016Article
- The C34 Peptide Fusion Inhibitor Binds to the Six-Helix Bundle Core Domain of HIV-1 gp41 by Displacement of the C-Terminal Helical Repeat Region.Biochemistry · 2015Article
- Single-chain protein mimetics of the N-terminal heptad-repeat region of gp41 with potential as anti-HIV-1 drugs.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Antibody to gp41 MPER alters functional properties of HIV-1 Env without complete neutralization.PLoS pathogens · 2014Article
- Sub-inhibitory concentrations of human α-defensin potentiate neutralizing antibodies against HIV-1 gp41 pre-hairpin intermediates in the presence of serum.PLoS pathogens · 2013Article
- Monoclonal antibody-based candidate therapeutics against HIV type 1.AIDS research and human retroviruses · 2012Review
- Structural mechanism of trimeric HIV-1 envelope glycoprotein activation.PLoS pathogens · 2012Article
- Amphipathic properties of HIV-1 gp41 fusion inhibitors.Current topics in medicinal chemistry · 2011Review
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Authors and funding
7 authors.
Funding
Abstract
During viral entry, HIV gp41 adopts a transient conformation called the "prehairpin intermediate" in which a highly conserved therapeutic target, the N-trimer, is exposed. Despite extensive discovery efforts, potent and broadly neutralizing antibodies that target the N-trimer are elusive. We previously demonstrated the N-trimer is protected by a steric block that prevents large proteins, such as antibodies, from accessing it. Here we further characterize the steric block and identify its source. To study the N-trimer steric accessibility, we produced two sets of C-peptide inhibitors (a potent inhibitor targeting the N-trimer) fused to cargo proteins of increasing size facing either the virus or cell side of the prehairpin intermediate. Both bulky inhibitor sets show a steric block, but the effect is more pronounced with virus-side cargo. Additionally, both sets maintain their potencies in a modified entry assay that removes possible sources of target cell steric hindrance. These results implicate a viral source, likely gp120, as the primary component of the steric block. In addition, we studied the steric accessibility of the "pocket" region of the N-trimer, a highly attractive drug and vaccine target. We demonstrated a pocket-specific antibody, D5, is more potent as an scFv than as a full-length IgG, suggesting the N-trimer steric restriction extends to the pocket. This characterization will facilitate the design of sterically restricted antigens that mimic the steric environment of the N-trimer in the prehairpin intermediate and are capable of inducing potent and broadly neutralizing antibodies that circumvent the N-trimer steric block.
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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.