Category: Assay Development and Screening
Entry of Nipah virus (NiV) into host cells is triggered by the binding of its attachment protein, G, to a cellular receptor, ephrinB2 or ephrinB3. Receptor contact induces G to activate the F fusion protein, which merges the virus and host membranes. Here we show using a combination of biophysical methods (second harmonic generation, conformation-specific antibody binding, hydrogen/deuterium exchange mass spectrometry, and electron microscopy) that monomeric ephrinB2 causes allosteric changes in Nipah G without large-scale conformational changes. Different responses in NiV G are induced by monomeric ephrinB2 versus a dimeric form, suggesting that oligomerization of ephrinB2 may be a requirement for full NiV G activation. These results suggest activation of an allosteric pathway through the NiV G protein upon initial ephrinB2 contact, prior to larger scale conformational changes that lead to F-triggering. These findings may open additional modes for targeting the Nipah virus entry apparatus in vaccines and therapeutics.
Joyce Wong– Postdoctoral Fellow, Stanford University, Stanford, CA