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Abstract
Hepatitis C virus (HCV) entry is dependent on host cell molecules tetraspanin CD81, scavenger receptor BI and tight junction proteins claudin-1 and occludin. We previously reported a role for CD81/claudin-1 receptor complexes in HCV entry; however, the molecular mechanism(s) driving association between the receptors is unknown. We explored the molecular interface between CD81 and claudin-1 using a combination of bioinformatic sequence-based modelling, site-directed mutagenesis and Fluorescent Resonance Energy Transfer (FRET) imaging methodologies. Structural modelling predicts the first extracellular loop of claudin-1 to have a flexible beta conformation and identifies a motif between amino acids 62-66 that interacts with CD81 residues T149, E152 and T153. FRET studies confirm a role for these CD81 residues in claudin-1 association and HCV infection. Importantly, mutation of these CD81 residues has minimal impact on protein conformation or HCV glycoprotein binding, highlighting a new functional domain of CD81 that is essential for virus entry.
Original language | English |
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Pages (from-to) | 1892-903 |
Number of pages | 12 |
Journal | Cellular Microbiology |
Volume | 14 |
Issue number | 12 |
Early online date | 25 Sept 2012 |
DOIs | |
Publication status | Published - Dec 2012 |
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Dive into the research topics of 'In silico directed mutagenesis identifies the CD81/claudin-1 hepatitis C virus receptor interface'. Together they form a unique fingerprint.Projects
- 2 Finished
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The Role of Hepatitis C Virus Glycoprotein-Receptor Polymorphism in Viral Pathogenesis
McKeating, J.
1/01/12 → 30/06/17
Project: Research Councils
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Mechanisms of Hepatitis C Virus Induced Hepatocyte Injury
McKeating, J. & Balfe, P.
1/10/09 → 30/09/12
Project: Research Councils