ArticlePLoS computational biology2020
Flexibility and intrinsic disorder are conserved features of hepatitis C virus E2 glycoprotein.
Article in PLoS computational biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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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Who cites it
19 citing papers in PubMed.
- Antibody responses to a highly conserved peptide in HCV E2 protein correlate with chronicity or spontaneous clearance of HCV infection.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Exploring the globoid cell leukodystrophy protein network and therapeutic interventions.Scientific reports · 2024Article
- Hepatitis C Virus E1E2 Structure, Diversity, and Implications for Vaccine Development.Viruses · 2024Review
- Prospects for developing an Hepatitis C virus E1E2-based nanoparticle vaccine.Reviews in medical virology · 2023Review
- Polyvalent immunization elicits a synergistic broadly neutralizing immune response to hypervariable region 1 variants of hepatitis C virus.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Hepatitis C virus hypervariable region 1 antibodies interrupt E2-SR-B1 interaction to suppress viral infection.iScience · 2023Article
- Induction of cross-neutralizing antibodies by a permuted hepatitis C virus glycoprotein nanoparticle vaccine candidate.Nature communications · 2022Article
- Structure of the hepatitis C virus E1E2 glycoprotein complex.Science (New York, N.Y.) · 2022Article
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- Intra-host analysis of hepaciviral glycoprotein evolution reveals signatures associated with viral persistence and clearance.Virus evolution · 2022Article
- Structural and Biophysical Characterization of the HCV E1E2 Heterodimer for Vaccine Development.Viruses · 2021Review
- Review
- From Structural Studies to HCV Vaccine Design.Viruses · 2021Review
- Mechanisms of Hepatitis C Virus Escape from Vaccine-Relevant Neutralizing Antibodies.Vaccines · 2021Review
- Optimized cell systems for the investigation of hepatitis C virus E1E2 glycoproteins.The Journal of general virology · 2021Article
- Structure-Based Design of Hepatitis C Virus E2 Glycoprotein Improves Serum Binding and Cross-Neutralization.Journal of virology · 2020Article
- HCV Glycoprotein Structure and Implications for B-Cell Vaccine Development.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The glycoproteins of hepatitis C virus, E1E2, are unlike any other viral fusion machinery yet described, and are the current focus of immunogen design in HCV vaccine development; thus, making E1E2 both scientifically and medically important. We used pre-existing, but fragmentary, structures to model a complete ectodomain of the major glycoprotein E2 from three strains of HCV. We then performed molecular dynamic simulations to explore the conformational landscape of E2, revealing a number of important features. Despite high sequence divergence, and subtle differences in the models, E2 from different strains behave similarly, possessing a stable core flanked by highly flexible regions, some of which perform essential functions such as receptor binding. Comparison with sequence data suggest that this consistent behaviour is conferred by a network of conserved residues that act as hinge and anchor points throughout E2. The variable regions (HVR-1, HVR-2 and VR-3) exhibit particularly high flexibility, and bioinformatic analysis suggests that HVR-1 is a putative intrinsically disordered protein region. Dynamic cross-correlation analyses demonstrate intramolecular communication and suggest that specific regions, such as HVR-1, can exert influence throughout E2. To support our computational approach we performed small-angle X-ray scattering with purified E2 ectodomain; this data was consistent with our MD experiments, suggesting a compact globular core with peripheral flexible regions. This work captures the dynamic behaviour of E2 and has direct relevance to the interaction of HCV with cell-surface receptors and neutralising antibodies.
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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.