TY - JOUR
T1 - Monomeric ephrinB2 binding induces allosteric changes in Nipah virus G that precede its full activation
AU - Wong, Joyce J.W.
AU - Young, Tracy A.
AU - Zhang, Jiayan
AU - Liu, Shiheng
AU - Leser, George P.
AU - Komives, Elizabeth A.
AU - Lamb, Robert A.
AU - Zhou, Z. Hong
AU - Salafsky, Joshua
AU - Jardetzky, Theodore S.
N1 - Funding Information:
We thank Hector Aguilar and Benhur Lee for providing the mAb213 and mAb45 antibodies. We thank Bason Clancy for preparation of Fig. 1b, c. This work was supported by NIH grants GM61050 (T.S.J.), GM07194 (Z.H.Z.), S10D012966 (E.A.K.) and the Howard Hughes Medical Institute (R.A.L.).
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-017-00863-3
DO - 10.1038/s41467-017-00863-3
M3 - Article
C2 - 28974687
AN - SCOPUS:85030462733
VL - 8
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 781
ER -