OmniVira

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

Joyce J W Wong1 Tracy A Young2 Jiayan Zhang3,4,5 Shiheng Liu4,5 George P Leser6,7 Elizabeth A Komives8 Robert A Lamb6,7 Z Hong Zhou4,5 Joshua Salafsky2 Theodore S Jardetzky9
Affiliations 9 institutions
  1. Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  2. Biodesy, Inc., South San Francisco, CA, 94080, USA.
  3. Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  4. Department of Microbiology, Immunology & Molecular Genetics, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  5. California NanoSystems Institute, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  6. Howard Hughes Medical Institute, Northwestern University, Evanston, IL, 60208-3500, USA.
  7. Department of Molecular Biosciences, Northwestern University, Evanston, IL, 60208-3500, USA.
  8. Department of Chemistry and Biochemistry, University of California San Diego, San Diego, CA, 92093, USA.
  9. Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, 94305, USA. [email protected].
PMID28974687 DOI10.1038/s41467-017-00863-3 Year2017 Journal Nature communications Nat Commun Languageeng Statusepublish

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.Nipah virus causes encephalitis in humans. Here the authors use a multidisciplinary approach to study the binding of the viral attachment protein G to its host receptor ephrinB2 and show that monomeric and dimeric receptors activate distinct conformational changes in G and discuss implications for receptor-activated virus entry.

Supporting text Virus Host Location
Allosteric Regulation 2 Antibodies, Monoclonal 26 Deuterium Exchange Measurement 1 Ephrin-B2 14 HEK293 Cells 61 Humans 1440 Mass Spectrometry 3 Mutant Proteins 15 Negative Staining 1 Nipah Virus 45 Protein Binding 193 Protein Multimerization 4 Viral Envelope Proteins 60 attachment protein G 8

Evidence records

1 total
Functional Mechanism
1 records · 1 evidence types
Evidence type Receptor Usage
1 records
OVE2726 Receptor Usage
Key finding

Nipah virus G protein binds to ephrinB2 and ephrinB3 receptors, inducing conformational changes that trigger fusion protein refolding and viral entry.

Virus
Nipah virus
Host
Not specified
Location
Not specified
Supporting text

Nipah virus is an emergent paramyxovirus that causes deadly encephalitis and respiratory infections in humans. The G protein binds to ephrin B2/3 receptors, inducing G conformational changes that trigger F protein refolding.

Method
hydrogen/deuterium exchange | second harmonic generation | electron microscopy
Receptors
ephrinB2 | ephrinB3
Host factors
F protein