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PDBsum entry 6t3f
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Viral protein
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PDB id
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6t3f
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Contents |
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454 a.a.
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215 a.a.
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201 a.a.
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PDB id:
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| Name: |
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Viral protein
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Title:
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Crystal structure nipah virus fusion glycoprotein in complex with a neutralising fab fragment
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Structure:
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Fusion glycoprotein f0. Chain: f. Synonym: protein f. Engineered: yes. Fab66 light chain. Chain: l. Engineered: yes. Fab66 heavy chain. Chain: h.
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Source:
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Nipah virus. Organism_taxid: 121791. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293t. Expression_system_atcc_number: crl-3216. Oryctolagus cuniculus. Rabbit. Organism_taxid: 9986.
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Resolution:
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3.20Å
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R-factor:
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0.215
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R-free:
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0.249
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Authors:
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V.A.Avanzato,R.Pryce,T.S.Walter,T.A.Bowden
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Key ref:
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V.A.Avanzato
et al.
(2019).
A structural basis for antibody-mediated neutralization of Nipah virus reveals a site of vulnerability at the fusion glycoprotein apex.
Proc Natl Acad Sci U S A,
116,
25057-25067.
PubMed id:
DOI:
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Date:
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10-Oct-19
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Release date:
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27-Nov-19
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PROCHECK
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Headers
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References
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Q9IH63
(FUS_NIPAV) -
Fusion glycoprotein F0 from Nipah virus
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Seq:
Struc:
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546 a.a.
454 a.a.*
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DOI no:
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Proc Natl Acad Sci U S A
116:25057-25067
(2019)
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PubMed id:
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A structural basis for antibody-mediated neutralization of Nipah virus reveals a site of vulnerability at the fusion glycoprotein apex.
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V.A.Avanzato,
K.Y.Oguntuyo,
M.Escalera-Zamudio,
B.Gutierrez,
M.Golden,
S.L.Kosakovsky Pond,
R.Pryce,
T.S.Walter,
J.Seow,
K.J.Doores,
O.G.Pybus,
V.J.Munster,
B.Lee,
T.A.Bowden.
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ABSTRACT
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Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes frequent
outbreaks of severe neurologic and respiratory disease in humans with high case
fatality rates. The 2 glycoproteins displayed on the surface of the virus, NiV-G
and NiV-F, mediate host-cell attachment and membrane fusion, respectively, and
are targets of the host antibody response. Here, we provide a molecular basis
for neutralization of NiV through antibody-mediated targeting of NiV-F.
Structural characterization of a neutralizing antibody (nAb) in complex with
trimeric prefusion NiV-F reveals an epitope at the membrane-distal domain III
(DIII) of the molecule, a region that undergoes substantial refolding during
host-cell entry. The epitope of this monoclonal antibody (mAb66) is primarily
protein-specific and we observe that glycosylation at the periphery of the
interface likely does not inhibit mAb66 binding to NiV-F. Further
characterization reveals that a Hendra virus-F-specific nAb (mAb36) and many
antibodies in an antihenipavirus-F polyclonal antibody mixture (pAb835) also
target this region of the molecule. Integrated with previously reported
paramyxovirus F-nAb structures, these data support a model whereby the
membrane-distal region of the F protein is targeted by the antibody-mediated
immune response across henipaviruses. Notably, our domain-specific sequence
analysis reveals no evidence of selective pressure at this region of the
molecule, suggestive that functional constraints prevent immune-driven sequence
variation. Combined, our data reveal the membrane-distal region of NiV-F as a
site of vulnerability on the NiV surface.
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