Author
Listed:
- Joyce J. W. Wong
(Stanford University School of Medicine)
- Tracy A. Young
(Biodesy, Inc.)
- Jiayan Zhang
(University of California Los Angeles
University of California Los Angeles
University of California Los Angeles)
- Shiheng Liu
(University of California Los Angeles
University of California Los Angeles)
- George P. Leser
(Northwestern University
Northwestern University)
- Elizabeth A. Komives
(University of California San Diego)
- Robert A. Lamb
(Northwestern University
Northwestern University)
- Z. Hong Zhou
(University of California Los Angeles
University of California Los Angeles)
- Joshua Salafsky
(Biodesy, Inc.)
- Theodore S. Jardetzky
(Stanford University School of Medicine)
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.
Suggested Citation
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, 2017.
"Monomeric ephrinB2 binding induces allosteric changes in Nipah virus G that precede its full activation,"
Nature Communications, Nature, vol. 8(1), pages 1-11, December.
Handle:
RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00863-3
DOI: 10.1038/s41467-017-00863-3
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