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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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References listed in PDB file
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Key reference
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Title
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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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Authors
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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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Ref.
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Proc Natl Acad Sci U S A, 2019,
116,
25057-25067.
[DOI no: ]
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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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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