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J Virol 2015 Jan 1;89(1):492-501

A View of the E2-CD81 Interface at the Binding Site of a Neutralizing Antibody against Hepatitis C Virus.

Harman C, Zhong L, Ma L, Liu P, Deng L, Zhao Z, Yan H, Struble E, Virata-Theimer ML, Zhang P

Abstract

Hepatitis C virus (HCV) glycoprotein E2 is considered a major target for generating neutralizing antibodies against HCV, primarily due to its role of engaging host entry factors such as CD81, a key cell surface protein associated with HCV entry. Based on a series of biochemical analyses, in combination with molecular docking, we present a description of a potential binding interface formed between the E2 protein and CD81. The virus side of this interface includes a hydrophobic helix motif comprised of residues W437LAGLF442, which encompasses the binding site of a neutralizing monoclonal antibody, mAb41. The helical conformation of this motif provides a structural framework for the positioning of residues, F442 and Y443, serving as contact points for the interaction with CD81. The cell side of this interface likewise involves a surface-exposed hydrophobic helix, namely the D-helix of CD81, which coincides with the binding site of 1D6, a monoclonal anti-CD81 antibody known to block HCV entry. Our illustration of this virus-host interface suggests an important role played by the W437LAGLF442 helix of the E2 protein in the hydrophobic interaction with the D-helix of CD81, thereby facilitating our understanding of the mechanism for the antibody-mediated neutralization of HCV. IMPORTANCE: Characterization of the interface established between the virus and host cells can provide important information towards the control of virus infections. The interface formed that enables hepatitis C virus (HCV) to infect human liver cells has not been well-understood because of the number of cell surface proteins, factors and conditions found to be associated with the infection process. Based on a series of biochemical analyses, in combination with molecular docking, we present such an interface, consisting of two hydrophobic helical structures from the HCV E2 surface glycoprotein and the CD81 protein, a major host cell receptor recognized by all HCV strains. Our study reveals the critical role played by the hydrophobic interactions in the formation of this virus-host interface, thereby contributing to our understanding of the mechanism for the antibody-mediated neutralization of HCV.


Category: Journal Article
PubMed ID: #25339761 DOI: 10.1128/JVI.01661-14
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2014-10-24 Entry Last Modified: 2015-02-07
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