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| | ==Crystal structure of HCMV glycoprotein B in complex with 1G2 Fab== | | ==Crystal structure of HCMV glycoprotein B in complex with 1G2 Fab== |
| - | <StructureSection load='5c6t' size='340' side='right' caption='[[5c6t]], [[Resolution|resolution]] 3.60Å' scene=''> | + | <StructureSection load='5c6t' size='340' side='right'caption='[[5c6t]], [[Resolution|resolution]] 3.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5c6t]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hcmvt Hcmvt] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5C6T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5C6T FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5c6t]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_herpesvirus_5_strain_Towne Human herpesvirus 5 strain Towne]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5C6T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5C6T FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <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]] 3.6Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gB, UL55 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10363 HCMVT])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5c6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c6t OCA], [http://pdbe.org/5c6t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5c6t RCSB], [http://www.ebi.ac.uk/pdbsum/5c6t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5c6t 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=5c6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5c6t OCA], [https://pdbe.org/5c6t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5c6t RCSB], [https://www.ebi.ac.uk/pdbsum/5c6t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5c6t ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GB_HCMVT GB_HCMVT]] Envelope glycoprotein that plays a role in host cell entry, cell to-cell virus transmission, and fusion of infected cells. May be involved in the initial attachment via binding to heparan sulfate together with the gM/gN complex that binds heparin with higher affinity. Interacts with host integrin ITGB1, PDGFRA and EGFR that likely serve as postattachment entry receptors. Participates also in the fusion of viral and cellular membranes leading to virus entry into the host cell. Membrane fusion is mediated by the fusion machinery composed at least of gB and the heterodimer gH/gL (By similarity). Viral ligand for CD209/DC-SIGN. This interaction allows capture of viral particles by dendritic (DCs) cells and subsequent virus transmission to permissive cells. DCs are professional antigen presenting cells, critical for host immunity by inducing specific immune responses against a broad variety of pathogens. They act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. CMV subverts the migration properties of dendritic cells to gain access to target organs or susceptible cells. | + | [https://www.uniprot.org/uniprot/GB_HCMVT GB_HCMVT] Envelope glycoprotein that plays a role in host cell entry, cell to-cell virus transmission, and fusion of infected cells. May be involved in the initial attachment via binding to heparan sulfate together with the gM/gN complex that binds heparin with higher affinity. Interacts with host integrin ITGB1, PDGFRA and EGFR that likely serve as postattachment entry receptors. Participates also in the fusion of viral and cellular membranes leading to virus entry into the host cell. Membrane fusion is mediated by the fusion machinery composed at least of gB and the heterodimer gH/gL (By similarity). Viral ligand for CD209/DC-SIGN. This interaction allows capture of viral particles by dendritic (DCs) cells and subsequent virus transmission to permissive cells. DCs are professional antigen presenting cells, critical for host immunity by inducing specific immune responses against a broad variety of pathogens. They act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. CMV subverts the migration properties of dendritic cells to gain access to target organs or susceptible cells. |
| | <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 5c6t" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5c6t" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Glycoproteins B and D|Glycoproteins B and D]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hcmvt]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Human herpesvirus 5 strain Towne]] |
| - | [[Category: Carfi, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Chandramouli, S]] | + | [[Category: Carfi A]] |
| - | [[Category: Ciferri, C]] | + | [[Category: Chandramouli S]] |
| - | [[Category: Settembre, E C]] | + | [[Category: Ciferri C]] |
| - | [[Category: Complex]] | + | [[Category: Settembre EC]] |
| - | [[Category: Cytomegalovirus]]
| + | |
| - | [[Category: Gb]]
| + | |
| - | [[Category: Glycoprotein b]]
| + | |
| - | [[Category: Viral protein-immue system complex]]
| + | |
| Structural highlights
Function
GB_HCMVT Envelope glycoprotein that plays a role in host cell entry, cell to-cell virus transmission, and fusion of infected cells. May be involved in the initial attachment via binding to heparan sulfate together with the gM/gN complex that binds heparin with higher affinity. Interacts with host integrin ITGB1, PDGFRA and EGFR that likely serve as postattachment entry receptors. Participates also in the fusion of viral and cellular membranes leading to virus entry into the host cell. Membrane fusion is mediated by the fusion machinery composed at least of gB and the heterodimer gH/gL (By similarity). Viral ligand for CD209/DC-SIGN. This interaction allows capture of viral particles by dendritic (DCs) cells and subsequent virus transmission to permissive cells. DCs are professional antigen presenting cells, critical for host immunity by inducing specific immune responses against a broad variety of pathogens. They act as sentinels in various tissues where they entrap pathogens and convey them to local lymphoid tissue or lymph node for establishment of immunity. CMV subverts the migration properties of dendritic cells to gain access to target organs or susceptible cells.
Publication Abstract from PubMed
Human cytomegalovirus (HCMV) poses a significant threat to immunocompromised individuals and neonates infected in utero. Glycoprotein B (gB), the herpesvirus fusion protein, is a target for neutralizing antibodies and a vaccine candidate due to its indispensable role in infection. Here we show the crystal structure of the HCMV gB ectodomain bound to the Fab fragment of 1G2, a neutralizing human monoclonal antibody isolated from a seropositive subject. The gB/1G2 interaction is dominated by aromatic residues in the 1G2 heavy chain CDR3 protruding into a hydrophobic cleft in the gB antigenic domain 5 (AD-5). Structural analysis and comparison with HSV gB suggest the location of additional neutralizing antibody binding sites on HCMV gB. Finally, immunoprecipitation experiments reveal that 1G2 can bind to HCMV virion gB suggesting that its epitope is exposed and accessible on the virus surface. Our data will support the development of vaccines and therapeutic antibodies against HCMV infection.
Structure of HCMV glycoprotein B in the postfusion conformation bound to a neutralizing human antibody.,Chandramouli S, Ciferri C, Nikitin PA, Calo S, Gerrein R, Balabanis K, Monroe J, Hebner C, Lilja AE, Settembre EC, Carfi A Nat Commun. 2015 Sep 14;6:8176. doi: 10.1038/ncomms9176. PMID:26365435[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chandramouli S, Ciferri C, Nikitin PA, Calo S, Gerrein R, Balabanis K, Monroe J, Hebner C, Lilja AE, Settembre EC, Carfi A. Structure of HCMV glycoprotein B in the postfusion conformation bound to a neutralizing human antibody. Nat Commun. 2015 Sep 14;6:8176. doi: 10.1038/ncomms9176. PMID:26365435 doi:http://dx.doi.org/10.1038/ncomms9176
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