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| | <StructureSection load='5ejb' size='340' side='right'caption='[[5ejb]], [[Resolution|resolution]] 3.20Å' scene=''> | | <StructureSection load='5ejb' size='340' side='right'caption='[[5ejb]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ejb]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Equine_morbillivirus Equine morbillivirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EJB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EJB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ejb]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Hendra_henipavirus Hendra henipavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EJB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EJB 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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">F ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=63330 Equine morbillivirus])</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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=5ejb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ejb OCA], [http://pdbe.org/5ejb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ejb RCSB], [http://www.ebi.ac.uk/pdbsum/5ejb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ejb ProSAT]</span></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=5ejb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ejb OCA], [https://pdbe.org/5ejb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ejb RCSB], [https://www.ebi.ac.uk/pdbsum/5ejb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ejb ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/FUS_HENDH FUS_HENDH] 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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Equine morbillivirus]] | + | [[Category: Hendra henipavirus]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Jardetzky, T S]] | + | [[Category: Jardetzky TS]] |
| - | [[Category: Lamb, R A]] | + | [[Category: Lamb RA]] |
| - | [[Category: Paterson, R G]] | + | [[Category: Paterson RG]] |
| - | [[Category: Wong, J W]] | + | [[Category: Wong JW]] |
| - | [[Category: Ectodomain]]
| + | |
| - | [[Category: Prefusion form]]
| + | |
| - | [[Category: Viral glycoprotein]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| Structural highlights
Function
FUS_HENDH 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
Hendra virus (HeV) is one of the two prototypical members of the Henipavirus genus of paramyxoviruses, which are designated biosafety level 4 (BSL-4) organisms due to the high mortality rate of Nipah virus (NiV) and HeV in humans. Paramyxovirus cell entry is mediated by the fusion protein, F, in response to binding of a host receptor by the attachment protein. During posttranslational processing, the fusion peptide of F is released and, upon receptor-induced triggering, inserts into the host cell membrane. As F undergoes a dramatic refolding from its prefusion to postfusion conformation, the fusion peptide brings the host and viral membranes together, allowing entry of the viral RNA. Here, we present the crystal structure of the prefusion form of the HeV F ectodomain. The structure shows very high similarity to the structure of prefusion parainfluenza virus 5 (PIV5) F, with the main structural differences in the membrane distal apical loops and the fusion peptide cleavage loop. Functional assays of mutants show that the apical loop can tolerate perturbation in length and surface residues without loss of function, except for residues involved in the stability and conservation of the F protein fold. Structure-based disulfide mutants were designed to anchor the fusion peptide to conformationally invariant residues of the F head. Two mutants were identified that inhibit F-mediated fusion by stabilizing F in its prefusion conformation.
Structure and stabilization of the Hendra virus F glycoprotein in its prefusion form.,Wong JJ, Paterson RG, Lamb RA, Jardetzky TS Proc Natl Acad Sci U S A. 2015 Dec 28. pii: 201523303. PMID:26712026[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wong JJ, Paterson RG, Lamb RA, Jardetzky TS. Structure and stabilization of the Hendra virus F glycoprotein in its prefusion form. Proc Natl Acad Sci U S A. 2015 Dec 28. pii: 201523303. PMID:26712026 doi:http://dx.doi.org/10.1073/pnas.1523303113
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