Adolescent Health in Myanmar
Support Burnet’s Adolescent Health Programs in Myanmar today.
Support Burnet’s Adolescent Health Programs in Myanmar today.
Support Burnet’s Adolescent Health Programs in Myanmar today.
Support Burnet’s Adolescent Health Programs in Myanmar today.
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.