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Literature detail

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].
PMID 28974687 2017 Nat Commun eng epublish
PubMed DOI Browse context

Article

Publication summary

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.

Allosteric Regulation Antibodies, Monoclonal Deuterium Exchange Measurement Ephrin-B2 HEK293 Cells Humans Mass Spectrometry Mutant Proteins Negative Staining Nipah Virus Protein Binding Protein Multimerization Viral Envelope Proteins attachment protein G

Structured evidence records

Evidence records

2 total
Receptor Usage 2 records
Receptor Usage Extraction confidence 0.97
Key finding

Nipah virus G attachment protein interacts with ephrinB2 and ephrinB3 receptors, and monomeric versus dimeric ephrinB2 induce distinct receptor-mediated conformational changes that activate viral entry.

Virus
NiV
Location
Not specified
Supporting text

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.

Method
second harmonic generation; hydrogen/deuterium exchange experiments; electron microscopy
Receptors
ephrinB2
Receptor Usage Extraction confidence 0.97
Key finding

Nipah virus G attachment protein binds ephrinB3 receptor and induces conformational changes that initiate F protein activation and receptor-mediated viral entry.

Virus
NiV
Location
Not specified
Supporting text

The G protein binds to ephrin B2/3 receptors, inducing G conformational changes that trigger F protein refolding.

Method
binding assay
Receptors
ephrinB3