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PDBsum entry 3d11
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References listed in PDB file
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Key reference
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Title
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Host cell recognition by the henipaviruses: crystal structures of the nipah g attachment glycoprotein and its complex with ephrin-B3.
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Authors
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K.Xu,
K.R.Rajashankar,
Y.P.Chan,
J.P.Himanen,
C.C.Broder,
D.B.Nikolov.
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Ref.
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Proc Natl Acad Sci U S A, 2008,
105,
9953-9958.
[DOI no: ]
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PubMed id
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Abstract
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Nipah virus (NiV) and Hendra virus are the type species of the highly pathogenic
paramyxovirus genus Henipavirus, which can cause severe respiratory disease and
fatal encephalitis infections in humans, with case fatality rates approaching
75%. NiV contains two envelope glycoproteins, the receptor-binding G
glycoprotein (NiV-G) that facilitates attachment to host cells and the fusion
(F) glycoprotein that mediates membrane merger. The henipavirus G glycoproteins
lack both hemagglutinating and neuraminidase activities and, instead, engage the
highly conserved ephrin-B2 and ephrin-B3 cell surface proteins as their entry
receptors. Here, we report the crystal structures of the NiV-G both in its
receptor-unbound state and in complex with ephrin-B3, providing, to our
knowledge, the first view of a paramyxovirus attachment complex in which a
cellular protein is used as the virus receptor. Complex formation generates an
extensive protein-protein interface around a protruding ephrin loop, which is
inserted in the central cavity of the NiV-G beta-propeller. Analysis of the
structural data reveals the molecular basis for the highly specific interactions
of the henipavirus G glycoproteins with only two members (ephrin-B2 and
ephrin-B3) of the very large ephrin family and suggests how they mediate in a
unique fashion both cell attachment and the initiation of membrane fusion during
the virus infection processes. The structures further suggest that the
NiV-G/ephrin interactions can be effectively targeted to disrupt viral entry and
provide the foundation for structure-based antiviral drug design.
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Figure 2.
Crystal structure of the NiV-G/ephrin-B3 complex. (A) Side
view of the NiV-G/ephrin-B3 complex. The β-strands of NiV-G are
colored in magenta, and the α-helices are in cyan. The
β-strands of ephrin-B3 are colored in yellow and the α-helices
are in red. The carbohydrate moieties, shown as stick models, do
not interact with ephrin-B3 but extend in the solvent. The N and
C termini of the molecules are labeled. (B) The molecular
surfaces of the henipavirus (cyan) and the parainfluenza virus
(magenta) attachment proteins along the top (or
receptor-binding) face of the molecules. The lower images are
close-up views of the receptor-binding pockets with the bound
receptor (ephrin-B3 G–H loop in yellow, sialic acid in green).
Only the G–H loop of ephrin-B3 is shown. In red are shown the
NiV-G residues that interact with ephrin-B3 residues outside of
the G–H loop, highlighting the polar region of the
NiV-G/ephrin interface.
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Figure 5.
Structure of the NiV-G/ephrin interface. Interacting residues
are labeled. (A) Salt bridges at the polar (peripheral) region
of the NiV-G/ephrin interface. NiV-G is in yellow and ephrin-B3
in gray. (B) The G–H ephrin-B3 loop bound to the NiV-G surface
channel. (C) The same surface in the unbound NiV-G molecule. The
position of the G–H ephrin-B3 loop is still shown to
illustrate that the binding pockets for ephrin residues P122,
L124, and W125 are already fully formed in the unbound
attachment protein and undergo little or no conformational
rearrangements upon ephrin binding. On the other hand, the Y120
binding pocket is only formed upon ephrin binding.
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