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| | ==RSV G peptide bound to Fab CB002.5== | | ==RSV G peptide bound to Fab CB002.5== |
| - | <StructureSection load='6bli' size='340' side='right' caption='[[6bli]], [[Resolution|resolution]] 2.12Å' scene=''> | + | <StructureSection load='6bli' size='340' side='right'caption='[[6bli]], [[Resolution|resolution]] 2.12Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6bli]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BLI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BLI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bli]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_respiratory_syncytial_virus_(strain_RSB6256) Human respiratory syncytial virus (strain RSB6256)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BLI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BLI FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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]] 2.12Å</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=6bli FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bli OCA], [http://pdbe.org/6bli PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bli RCSB], [http://www.ebi.ac.uk/pdbsum/6bli PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bli ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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=6bli FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bli OCA], [https://pdbe.org/6bli PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bli RCSB], [https://www.ebi.ac.uk/pdbsum/6bli PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bli ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GLYC_HRSV6 GLYC_HRSV6]] Attaches the virion to the host cell membrane by interacting with heparan sulfate, initiating the infection. Interacts with host CX3CR1, the receptor for the CX3C chemokine fractalkine, to modulate the immune response and facilitate infection. Unlike the other paramyxovirus attachment proteins, lacks both neuraminidase and hemagglutinating activities (By similarity). Secreted glycoprotein G helps RSV escape antibody-dependent restriction of replication by acting as an antigen decoy and by modulating the activity of leukocytes bearing Fcgamma receptors. | + | [https://www.uniprot.org/uniprot/GLYC_HRSV6 GLYC_HRSV6] Attaches the virion to the host cell membrane by interacting with heparan sulfate, initiating the infection. Interacts with host CX3CR1, the receptor for the CX3C chemokine fractalkine, to modulate the immune response and facilitate infection. Unlike the other paramyxovirus attachment proteins, lacks both neuraminidase and hemagglutinating activities (By similarity). Secreted glycoprotein G helps RSV escape antibody-dependent restriction of replication by acting as an antigen decoy and by modulating the activity of leukocytes bearing Fcgamma receptors. |
| | <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 6bli" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6bli" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Antibody 3D structures|Antibody 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Jones, H G]] | + | [[Category: Large Structures]] |
| - | [[Category: Langedijk, J P]] | + | [[Category: Jones HG]] |
| - | [[Category: McLellan, J S]] | + | [[Category: Langedijk JP]] |
| - | [[Category: Antibody]] | + | [[Category: McLellan JS]] |
| - | [[Category: Viral attachment protein]]
| + | |
| - | [[Category: Viral protein]]
| + | |
| - | [[Category: Viral protein-immune system complex]]
| + | |
| Structural highlights
Function
GLYC_HRSV6 Attaches the virion to the host cell membrane by interacting with heparan sulfate, initiating the infection. Interacts with host CX3CR1, the receptor for the CX3C chemokine fractalkine, to modulate the immune response and facilitate infection. Unlike the other paramyxovirus attachment proteins, lacks both neuraminidase and hemagglutinating activities (By similarity). Secreted glycoprotein G helps RSV escape antibody-dependent restriction of replication by acting as an antigen decoy and by modulating the activity of leukocytes bearing Fcgamma receptors.
Publication Abstract from PubMed
Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants and the elderly, and yet there remains no effective treatment or vaccine. The surface of the virion is decorated with the fusion glycoprotein (RSV F) and the attachment glycoprotein (RSV G), which binds to CX3CR1 on human airway epithelial cells to mediate viral attachment and subsequent infection. RSV G is a major target of the humoral immune response, and antibodies that target the central conserved region of G have been shown to neutralize both subtypes of RSV and to protect against severe RSV disease in animal models. However, the molecular underpinnings for antibody recognition of this region have remained unknown. Therefore, we isolated two human antibodies directed against the central conserved region of RSV G and demonstrated that they neutralize RSV infection of human bronchial epithelial cell cultures in the absence of complement. Moreover, the antibodies protected cotton rats from severe RSV disease. Both antibodies bound with high affinity to a secreted form of RSV G as well as to a peptide corresponding to the unglycosylated central conserved region. High-resolution crystal structures of each antibody in complex with the G peptide revealed two distinct conformational epitopes that require proper folding of the cystine noose located in the C-terminal part of the central conserved region. Comparison of these structures with the structure of fractalkine (CX3CL1) alone or in complex with a viral homolog of CX3CR1 (US28) suggests that RSV G would bind to CX3CR1 in a mode that is distinct from that of fractalkine. Collectively, these results build on recent studies demonstrating the importance of RSV G in antibody-mediated protection from severe RSV disease, and the structural information presented here should guide the development of new vaccines and antibody-based therapies for RSV.
Structural basis for recognition of the central conserved region of RSV G by neutralizing human antibodies.,Jones HG, Ritschel T, Pascual G, Brakenhoff JPJ, Keogh E, Furmanova-Hollenstein P, Lanckacker E, Wadia JS, Gilman MSA, Williamson RA, Roymans D, van 't Wout AB, Langedijk JP, McLellan JS PLoS Pathog. 2018 Mar 6;14(3):e1006935. doi: 10.1371/journal.ppat.1006935., eCollection 2018 Mar. PMID:29509814[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jones HG, Ritschel T, Pascual G, Brakenhoff JPJ, Keogh E, Furmanova-Hollenstein P, Lanckacker E, Wadia JS, Gilman MSA, Williamson RA, Roymans D, van 't Wout AB, Langedijk JP, McLellan JS. Structural basis for recognition of the central conserved region of RSV G by neutralizing human antibodies. PLoS Pathog. 2018 Mar 6;14(3):e1006935. doi: 10.1371/journal.ppat.1006935., eCollection 2018 Mar. PMID:29509814 doi:http://dx.doi.org/10.1371/journal.ppat.1006935
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