Monomeric ephrinB2 binding induces allosteric changes in Nipah virus G that precede its full activation

Joyce J.W. Wong, Tracy A. Young, Jiayan Zhang, Shiheng Liu, George P. Leser, Elizabeth A. Komives, Robert A. Lamb, Z. Hong Zhou, Joshua Salafsky, Theodore S. Jardetzky*

*Corresponding author for this work

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Nipah virus is an emergent paramyxovirus that causes deadly encephalitis and respiratory infections in humans. Two glycoproteins coordinate the infection of host cells, an attachment protein (G), which binds to cell surface receptors, and a fusion (F) protein, which carries out the process of virus-cell membrane fusion. The G protein binds to ephrin B2/3 receptors, inducing G conformational changes that trigger F protein refolding. Using an optical approach based on second harmonic generation, we show that monomeric and dimeric receptors activate distinct conformational changes in G. The monomeric receptor-induced changes are not detected by conformation-sensitive monoclonal antibodies or through electron microscopy analysis of G:ephrinB2 complexes. However, hydrogen/deuterium exchange experiments confirm the second harmonic generation observations and reveal allosteric changes in the G receptor binding and F-activating stalk domains, providing insights into the pathway of receptor-activated virus entry.

Original languageEnglish (US)
Article number781
JournalNature communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Wong, J. J. W., Young, T. A., Zhang, J., Liu, S., Leser, G. P., Komives, E. A., Lamb, R. A., Zhou, Z. H., Salafsky, J., & Jardetzky, T. S. (2017). Monomeric ephrinB2 binding induces allosteric changes in Nipah virus G that precede its full activation. Nature communications, 8(1), [781]. https://doi.org/10.1038/s41467-017-00863-3