Journal article
A novel receptor-induced activation site in the Nipah virus attachment glycoprotein (G) involved in triggering the fusion glycoprotein (F)
The Journal of biological chemistry, Vol.284(3), pp.1628-1635
01/16/2009
Handle:
https://hdl.handle.net/2376/104060
PMID: 19019819
Abstract
Cellular entry of paramyxoviruses requires the coordinated action of both the attachment (G/H/HN) and fusion (F) glycoproteins, but how receptor binding activates G to trigger F-mediated fusion during viral entry is not known. Here, we identify a receptor (ephrinB2)-induced allosteric activation site in Nipah virus (NiV) G involved in triggering F-mediated fusion. We first generated a conformational monoclonal antibody (monoclonal antibody 45 (Mab45)) whose binding to NiV-G was enhanced upon NiV-G-ephrinB2 binding. However, Mab45 also inhibited viral entry, and its receptor binding-enhanced (RBE) epitope was temperature-dependent, suggesting that the Mab45 RBE epitope on G may be involved in triggering F. The Mab45 RBE epitope was mapped to the base of the globular domain (beta6S4/beta1H1). Alanine scan mutants within this region that did not exhibit this RBE epitope were also non-fusogenic despite their ability to bind ephrinB2, oligomerize, and associate with F at wild-type (WT) levels. Although circular dichroism revealed conformational changes in the soluble ectodomain of WT NiV-G upon ephrinB2 addition, no such changes were detected with soluble RBE epitope mutants or short-stalk G mutants. Additionally, WT G, but not a RBE epitope mutant, could dissociate from F upon ephrinB2 engagement. Finally, using a biotinylated HR2 peptide to detect pre-hairpin intermediate formation, a cardinal feature of F-triggering, we showed that ephrinB2 binding to WT G, but not the RBE-epitope mutants, could trigger F. In sum, we implicate the coordinated interaction between the base of NiV-G globular head domain and the stalk domain in mediating receptor-induced F triggering during viral entry.
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Details
- Title
- A novel receptor-induced activation site in the Nipah virus attachment glycoprotein (G) involved in triggering the fusion glycoprotein (F)
- Creators
- Hector C Aguilar - Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA. haguilar@ucla.eduZeynep Akyol AtamanVanessa AspericuetaAngela Q FangMatthew StroudOscar A NegreteRichard A KammererBenhur Lee
- Publication Details
- The Journal of biological chemistry, Vol.284(3), pp.1628-1635
- Publisher
- United States
- Grant note
- AI069317 / NIAID NIH HHS AI070495 / NIAID NIH HHS U01 AI070495 / NIAID NIH HHS AI060694 / NIAID NIH HHS P30 CA016042 / NCI NIH HHS R01 AI069317 / NIAID NIH HHS P30 AI028697 / NIAID NIH HHS
- Identifiers
- 99900546562401842
- Language
- English
- Resource Type
- Journal article