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| | <StructureSection load='3ixt' size='340' side='right'caption='[[3ixt]], [[Resolution|resolution]] 2.75Å' scene=''> | | <StructureSection load='3ixt' size='340' side='right'caption='[[3ixt]], [[Resolution|resolution]] 2.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ixt]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_respiratory_syncytial_virus Human respiratory syncytial virus] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IXT OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3IXT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ixt]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_respiratory_syncytial_virus_A2 Human respiratory syncytial virus A2] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IXT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IXT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 2.75Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></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=3ixt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ixt OCA], [http://pdbe.org/3ixt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ixt RCSB], [http://www.ebi.ac.uk/pdbsum/3ixt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ixt 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=3ixt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ixt OCA], [https://pdbe.org/3ixt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ixt RCSB], [https://www.ebi.ac.uk/pdbsum/3ixt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ixt ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FUS_HRSVA FUS_HRSVA]] 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 (protein F) interacts with glycoprotein G at the virion surface. Upon binding of G to heparan sulfate, the hydrophobic fusion peptide is unmasked and interacts with the cellular membrane, inducing the fusion between host cell and virion membranes. Notably, RSV fusion protein is able to interact directly with heparan sulfate and therefore actively participates in virus attachment. Furthermore, the F2 subunit was identifed as the major determinant of RSV host cell specificity. Later in infection, proteins F expressed at the plasma membrane of infected cells mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis. The fusion protein is also able to trigger p53-dependent apoptosis.<ref>PMID:12663767</ref> <ref>PMID:18216092</ref> | + | [https://www.uniprot.org/uniprot/FUS_HRSVA FUS_HRSVA] 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 (protein F) interacts with glycoprotein G at the virion surface. Upon binding of G to heparan sulfate, the hydrophobic fusion peptide is unmasked and interacts with the cellular membrane, inducing the fusion between host cell and virion membranes. Notably, RSV fusion protein is able to interact directly with heparan sulfate and therefore actively participates in virus attachment. Furthermore, the F2 subunit was identifed as the major determinant of RSV host cell specificity. Later in infection, proteins F expressed at the plasma membrane of infected cells mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis. The fusion protein is also able to trigger p53-dependent apoptosis.<ref>PMID:12663767</ref> <ref>PMID:18216092</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human respiratory syncytial virus]] | + | [[Category: Human respiratory syncytial virus A2]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Chen, M]] | + | [[Category: Chen M]] |
| - | [[Category: Graham, B S]] | + | [[Category: Graham BS]] |
| - | [[Category: Kim, A]] | + | [[Category: Kim A]] |
| - | [[Category: Kwong, P D]] | + | [[Category: Kwong PD]] |
| - | [[Category: McLellan, J S]] | + | [[Category: McLellan JS]] |
| - | [[Category: Yang, Y]] | + | [[Category: Yang Y]] |
| - | [[Category: Cell membrane]]
| + | |
| - | [[Category: Cleavage on pair of basic residue]]
| + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Disulfide bond]]
| + | |
| - | [[Category: Envelope protein]]
| + | |
| - | [[Category: Fab]]
| + | |
| - | [[Category: Fusion protein]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Lipoprotein]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Monoclonal]]
| + | |
| - | [[Category: Motavizumab]]
| + | |
| - | [[Category: Palmitate]]
| + | |
| - | [[Category: Rsv]]
| + | |
| - | [[Category: Synagi]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| - | [[Category: Virion]]
| + | |
| Structural highlights
Function
FUS_HRSVA 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 (protein F) interacts with glycoprotein G at the virion surface. Upon binding of G to heparan sulfate, the hydrophobic fusion peptide is unmasked and interacts with the cellular membrane, inducing the fusion between host cell and virion membranes. Notably, RSV fusion protein is able to interact directly with heparan sulfate and therefore actively participates in virus attachment. Furthermore, the F2 subunit was identifed as the major determinant of RSV host cell specificity. Later in infection, proteins F expressed at the plasma membrane of infected cells mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis. The fusion protein is also able to trigger p53-dependent apoptosis.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Motavizumab is approximately tenfold more potent than its predecessor, palivizumab (Synagis), the FDA-approved monoclonal antibody used to prevent respiratory syncytial virus (RSV) infection. The structure of motavizumab in complex with a 24-residue peptide corresponding to its epitope on the RSV fusion (F) glycoprotein reveals the structural basis for this greater potency. Modeling suggests that motavizumab recognizes a different quaternary configuration of the F glycoprotein than that observed in a homologous structure.
Structural basis of respiratory syncytial virus neutralization by motavizumab.,McLellan JS, Chen M, Kim A, Yang Y, Graham BS, Kwong PD Nat Struct Mol Biol. 2010 Feb;17(2):248-50. Epub 2010 Jan 24. PMID:20098425[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schlender J, Zimmer G, Herrler G, Conzelmann KK. Respiratory syncytial virus (RSV) fusion protein subunit F2, not attachment protein G, determines the specificity of RSV infection. J Virol. 2003 Apr;77(8):4609-16. PMID:12663767
- ↑ Eckardt-Michel J, Lorek M, Baxmann D, Grunwald T, Keil GM, Zimmer G. The fusion protein of respiratory syncytial virus triggers p53-dependent apoptosis. J Virol. 2008 Apr;82(7):3236-49. Epub 2008 Jan 23. PMID:18216092 doi:JVI.01887-07
- ↑ McLellan JS, Chen M, Kim A, Yang Y, Graham BS, Kwong PD. Structural basis of respiratory syncytial virus neutralization by motavizumab. Nat Struct Mol Biol. 2010 Feb;17(2):248-50. Epub 2010 Jan 24. PMID:20098425 doi:10.1038/nsmb.1723
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