Abstract
Herpes simplex virus (HSV) infection requires binding of the viral envelope glycoprotein D (gD) to cell surface receptors. We report the X-ray structures of a soluble, truncated ectodomain of gD both alone and in complex with the ectodomain of its cellular receptor HveA. Two bound anions suggest possible binding sites for another gD receptor, a 3-O-sulfonated heparan sulfate. Unexpectedly, the structures reveal a V-like immunoglobulin (Ig) fold at the core of gD that is closely related to cellular adhesion molecules and flanked by large N- and C-terminal extensions. The receptor binding segment of gD, an N-terminal hairpin, appears conformationally flexible, suggesting that a conformational change accompanying binding might be part of the viral entry mechanism.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Binding Sites
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Crystallography, X-Ray
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Humans
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Ions / metabolism*
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Models, Molecular
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Molecular Sequence Data
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Protein Binding
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Protein Conformation
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Protein Structure, Tertiary
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Receptors, Tumor Necrosis Factor / chemistry*
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Receptors, Tumor Necrosis Factor / metabolism
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Receptors, Tumor Necrosis Factor, Member 14
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Receptors, Virus / chemistry*
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Receptors, Virus / metabolism
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Sequence Alignment
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Viral Envelope Proteins / chemistry*
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Viral Envelope Proteins / metabolism
Substances
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Ions
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Member 14
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Receptors, Virus
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TNFRSF14 protein, human
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Viral Envelope Proteins
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glycoprotein D, Human herpesvirus 1