Abstract
The binding of hepatitis C virus glycoprotein E2 to the large extracellular loop (LEL) of CD81 has been shown to modulate human T-cell and NK cell activity in vitro. Using random mutagenesis of a chimera of maltose-binding protein and LEL residues 113 to 201, we have determined that the E2-binding site on CD81 comprises residues Ile(182), Phe(186), Asn(184), and Leu(162). These findings reveal an E2-binding surface of approximately 806 A(2) and potential target sites for the development of small-molecule inhibitors of E2 binding.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / chemistry
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Antigens, CD / genetics
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Antigens, CD / metabolism*
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Binding Sites
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Cell Line, Transformed
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Hepacivirus / metabolism*
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Hepatitis C Antigens / metabolism*
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Humans
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Models, Molecular
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Mutagenesis
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Protein Structure, Tertiary
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Tetraspanin 28
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Viral Envelope Proteins / metabolism*
Substances
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Antigens, CD
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CD81 protein, human
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Hepatitis C Antigens
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Membrane Proteins
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Recombinant Fusion Proteins
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Tetraspanin 28
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Viral Envelope Proteins
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glycoprotein E2, Hepatitis C virus