ArticlePloS one2013
Stabilizing exposure of conserved epitopes by structure guided insertion of disulfide bond in HIV-1 envelope glycoprotein.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Strategic Optimization of the Middle Domain IIIA in RBP-Albumin IIIA-IB Fusion Protein to Enhance Productivity and Thermostability.International journal of molecular sciences · 2024Article
- Optimizing the Amino Acid Sequence Enhances the Productivity and Bioefficacy of the RBP-Albumin Fusion Protein.Bioengineering (Basel, Switzerland) · 2024Article
- A reverse vaccinology approach on transmembrane carbonic anhydrases from Plasmodium species as vaccine candidates for malaria prevention.Malaria journal · 2022Article
- Review
- Characterization and Immunogenicity of HIV Envelope gp140 ZeraFrontiers in bioengineering and biotechnology · 2020Article
- Disulfide Bond Characterization of Endogenous IgG3 Monoclonal Antibodies Using LC-MS: An Investigation of IgG3 Disulfide-mediated Isoforms.Analytical methods : advancing methods and applications · 2016Article
- Paring Down HIV Env: Design and Crystal Structure of a Stabilized Inner Domain of HIV-1 gp120 Displaying a Major ADCC Target of the A32 Region.Structure (London, England : 1993) · 2016Article
- Range of CD4-Bound Conformations of HIV-1 gp120, as Defined Using Conditional CD4-Induced Antibodies.Journal of virology · 2016Article
- Article
- Native Conformation and Canonical Disulfide Bond Formation Are Interlinked Properties of HIV-1 Env Glycoproteins.Journal of virology · 2015Article
- Influences on the Design and Purification of Soluble, Recombinant Native-Like HIV-1 Envelope Glycoprotein Trimers.Journal of virology · 2015Article
- Protein Crystallography in Vaccine Research and Development.International journal of molecular sciences · 2015Review
- CD4 mimetics sensitize HIV-1-infected cells to ADCC.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Antigenic requirement for Gag in a vaccine that protects against high-dose mucosal challenge with simian immunodeficiency virus.Virology · 2015Article
- Hyperglycosylated stable core immunogens designed to present the CD4 binding site are preferentially recognized by broadly neutralizing antibodies.Journal of virology · 2014Article
- CD4-mimetic small molecules sensitize human immunodeficiency virus to vaccine-elicited antibodies.Journal of virology · 2014Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Entry of HIV-1 into target cells requires binding of the viral envelope glycoprotein (Env) to cellular receptors and subsequent conformational changes that culminates in fusion of viral and target cell membranes. Recent structural information has revealed that these conformational transitions are regulated by three conserved but potentially flexible layers stacked between the receptor-binding domain (gp120) and the fusion arm (gp41) of Env. We hypothesized that artificial insertion of a covalent bond will 'snap' Env into a conformation that is less mobile and stably expose conserved sites. Therefore, we analyzed the interface between these gp120 layers (layers 1, 2 and 3) and identified residues that may form disulfide bonds when substituted with cysteines. We subsequently probed the structures of the resultant mutant gp120 proteins by assaying their binding to a variety of ligands using Surface Plasmon Resonance (SPR) assay. We found that a single disulfide bond strategically inserted between the highly conserved layers 1 and 2 (C65-C115) is able to 'lock' gp120 in a CD4 receptor bound conformation (in the absence of CD4), as indicated by the lower dissociation constant (Kd) for the CD4-induced (CD4i) epitope binding 17b antibody. When disulfide-stabilized monomeric (gp120) and trimeric (gp140) Envs were used to immunize rabbits, they were found to elicit a higher proportion of antibodies directed against both CD4i and CD4 binding site epitopes than the wild-type proteins. These results demonstrate that structure-guided stabilization of inter-layer interactions within HIV-1 Env can be used to expose conserved epitopes and potentially overcome the sequence diversity of these molecules.
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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.