Evidence of a Potential Receptor-binding Site on the Nipah Virus G Protein (Niv-g): Identification of Globular Head Residues with a Role in Fusion Promotion and Their Localization on an Niv-g Structural Model.
From: Molecular Basis of Paramyxovirus Entry, INSERM U404, Centre d’Etudes de Recherche en Virologie et Immunologie, IFR 128 Biosciences Lyon-Gerland, 21 avenue Tony Garnier, 69365 Lyon cedex 07, France.
Journal of virology
- Publish Date: Aug 2006
- ISSN: 0022-538X
- Volume: 80
- Issue: 15
- Pages: 7546-54
- Medium: Print
- Language: English
- Citation (JAMA): Guillaume Vanessa, Aslan Hamide, Ainouze Michelle, et al. Evidence of a Potential Receptor-binding Site on the Nipah Virus G Protein (Niv-g): Identification of Globular Head Residues with a Role in Fusion Promotion and Their Localization on an Niv-g Structural Model.. J. Virol. Aug 2006;80:7546-54
Abstract
As a preliminary to the localization of the receptor-binding site(s) on the Nipah virus (NiV) glycoprotein (NiV-G), we have undertaken the identification of NiV-G residues that play a role in fusion promotion. To achieve this, we have used two strategies. First, as NiV and Hendra virus (HeV) share a common receptor and their cellular tropism is similar, we hypothesized that residues functioning in receptor attachment could be conserved between their respective G proteins. Our initial strategy was to target charged residues (which can be expected to be at the surface of the protein) conserved between the NiV-G and HeV-G globular heads. Second, we generated NiV variants that escaped neutralization by anti-NiV-G monoclonal antibodies (MAbs) that neutralize NiV both in vitro and in vivo, likely by blocking receptor attachment. The sequencing of such “escape mutants” identified NiV-G residues present in the epitopes to which the neutralizing MAbs are directed. Residues identified via these two strategies whose mutation had an effect on fusion promotion were localized on a new structural model for the NiV-G protein. Our results suggest that seven NiV-G residues, including one (E533) that was identified using both strategies, form a contiguous site on the top of the globular head that is implicated in ephrinB2 binding. This site commences near the shallow depression in the center of the top surface of the globular head and extends to the rim of the barrel-like structure on the top loops of beta-sheet 5. The topology of this site is strikingly similar to that proposed to form the SLAM receptor site on another paramyxovirus attachment protein, that of the measles virus hemagglutinin.
Mesh Headings (Keywords): Amino Acid Sequence, Animals, Antibodies, Monoclonal, Binding Sites, CHO Cells, Cercopithecus aethiops, Cricetinae, Cricetulus, Ephrin-B2, Humans, Membrane Fusion, Models, Molecular, Molecular Sequence Data, Mutation, Nipah Virus, Receptors, Cell Surface, Sequence Homology, Amino Acid, Vero Cells, Viral Envelope Proteins
Check for Full Text / PubMed Unique Identifier (PMID): 16840334
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