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| | <StructureSection load='6t3f' size='340' side='right'caption='[[6t3f]], [[Resolution|resolution]] 3.20Å' scene=''> | | <StructureSection load='6t3f' size='340' side='right'caption='[[6t3f]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6t3f]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/European_rabbit European rabbit] and [http://en.wikipedia.org/wiki/Nipav Nipav]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T3F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6T3F FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6t3f]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Henipavirus_nipahense Henipavirus nipahense] and [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6T3F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6T3F FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</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=6t3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t3f OCA], [http://pdbe.org/6t3f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6t3f RCSB], [http://www.ebi.ac.uk/pdbsum/6t3f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6t3f ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6t3f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6t3f OCA], [https://pdbe.org/6t3f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6t3f RCSB], [https://www.ebi.ac.uk/pdbsum/6t3f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6t3f ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FUS_NIPAV 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). | + | [https://www.uniprot.org/uniprot/FUS_NIPAV 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). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6t3f" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6t3f" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: European rabbit]] | + | [[Category: Henipavirus nipahense]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Nipav]] | + | [[Category: Oryctolagus cuniculus]] |
| - | [[Category: Avanzato, V A]] | + | [[Category: Avanzato VA]] |
| - | [[Category: Bowden, T A]] | + | [[Category: Bowden TA]] |
| - | [[Category: Pryce, R]] | + | [[Category: Pryce R]] |
| - | [[Category: Walter, T S]] | + | [[Category: Walter TS]] |
| - | [[Category: Antibody]]
| + | |
| - | [[Category: Fab]]
| + | |
| - | [[Category: Fusion protein]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| Structural highlights
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) 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.
A structural basis for antibody-mediated neutralization of Nipah virus reveals a site of vulnerability at the fusion glycoprotein apex.,Avanzato VA, Oguntuyo KY, Escalera-Zamudio M, Gutierrez B, Golden M, Kosakovsky Pond SL, Pryce R, Walter TS, Seow J, Doores KJ, Pybus OG, Munster VJ, Lee B, Bowden TA Proc Natl Acad Sci U S A. 2019 Nov 25. pii: 1912503116. doi:, 10.1073/pnas.1912503116. PMID:31767754[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Avanzato VA, Oguntuyo KY, Escalera-Zamudio M, Gutierrez B, Golden M, Kosakovsky Pond SL, Pryce R, Walter TS, Seow J, Doores KJ, Pybus OG, Munster VJ, Lee B, Bowden TA. 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. 2019 Nov 25. pii: 1912503116. doi:, 10.1073/pnas.1912503116. PMID:31767754 doi:http://dx.doi.org/10.1073/pnas.1912503116
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