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6tys

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A potent cross-neutralizing antibody targeting the fusion glycoprotein inhibits Nipah virus and Hendra virus infection

6tys, resolution 3.50Å

Structural highlights

6tys is a 9 chain structure with sequence from Lk3 transgenic mice and Nipav. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	Igkv12-98 (LK3 transgenic mice)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[FUS_NIPAV] Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and plasma cell membrane fusion, the heptad repeat (HR) regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and plasma cell membranes. Directs fusion of viral and cellular membranes leading to delivery of the nucleocapsid into the cytoplasm. This fusion is pH independent and occurs directly at the outer cell membrane. The trimer of F1-F2 (F protein) probably interacts with HN at the virion surface. Upon HN binding to its cellular receptor, the hydrophobic fusion peptide is unmasked and interacts with the cellular membrane, inducing the fusion between cell and virion membranes. Later in infection, F proteins expressed at the plasma membrane of infected cells could mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis (By similarity).

Publication Abstract from PubMed

Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness with fatality rates of 50-100%. No vaccines or licensed therapeutics currently exist to protect humans against NiV or HeV. HNVs enter host cells by fusing the viral and cellular membranes via the concerted action of the attachment (G) and fusion (F) glycoproteins, the main targets of the humoral immune response. Here, we describe the isolation and humanization of a potent monoclonal antibody cross-neutralizing NiV and HeV. Cryo-electron microscopy, triggering and fusion studies show the antibody binds to a prefusion-specific quaternary epitope, conserved in NiV F and HeV F glycoproteins, and prevents membrane fusion and viral entry. This work supports the importance of the HNV prefusion F conformation for eliciting a robust immune response and paves the way for using this antibody for prophylaxis and post-exposure therapy with NiV- and HeV-infected individuals.

An antibody against the F glycoprotein inhibits Nipah and Hendra virus infections.,Dang HV, Chan YP, Park YJ, Snijder J, Da Silva SC, Vu B, Yan L, Feng YR, Rockx B, Geisbert TW, Mire CE, Broder CC, Veesler D Nat Struct Mol Biol. 2019 Sep 30. pii: 10.1038/s41594-019-0308-9. doi:, 10.1038/s41594-019-0308-9. PMID:31570878^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Dang HV, Chan YP, Park YJ, Snijder J, Da Silva SC, Vu B, Yan L, Feng YR, Rockx B, Geisbert TW, Mire CE, Broder CC, Veesler D. An antibody against the F glycoprotein inhibits Nipah and Hendra virus infections. Nat Struct Mol Biol. 2019 Sep 30. pii: 10.1038/s41594-019-0308-9. doi:, 10.1038/s41594-019-0308-9. PMID:31570878 doi:http://dx.doi.org/10.1038/s41594-019-0308-9

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6tys"

@@ Line 1: / Line 1: @@
 ==A potent cross-neutralizing antibody targeting the fusion glycoprotein inhibits Nipah virus and Hendra virus infection==
-<StructureSection load='6tys' size='340' side='right'caption='[[6tys]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
+<SX load='6tys' size='340' side='right' viewer='molstar' caption='[[6tys]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6tys]] is a 9 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice] and [http://en.wikipedia.org/wiki/Nipav Nipav]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TYS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6TYS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6tys]] is a 9 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice] and [http://en.wikipedia.org/wiki/Nipav Nipav]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TYS OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6TYS FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Igkv12-98 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6tys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tys OCA], [http://pdbe.org/6tys PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tys RCSB], [http://www.ebi.ac.uk/pdbsum/6tys PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tys ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6tys FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tys OCA], [http://pdbe.org/6tys PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6tys RCSB], [http://www.ebi.ac.uk/pdbsum/6tys PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6tys ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 22: / Line 22: @@
 <references/>
 __TOC__
-</StructureSection>
+</SX>
 [[Category: Large Structures]]
 [[Category: Lk3 transgenic mice]]

6tys

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Current revision

A potent cross-neutralizing antibody targeting the fusion glycoprotein inhibits Nipah virus and Hendra virus infection

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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