5cxf

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the extracellular domain of glycoprotein B from Human Cytomegalovirus

Structural highlights

5cxf is a 3 chain structure with sequence from Human herpesvirus 5 strain AD169. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.602Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GB_HCMVA 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.^[1] ^[2] 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 (By similarity).

Publication Abstract from PubMed

Human cytomegalovirus (HCMV), a dsDNA, enveloped virus, is a ubiquitous pathogen that establishes lifelong latent infections and caused disease in persons with compromised immune systems, e.g., organ transplant recipients or AIDS patients. HCMV is also a leading cause of congenital viral infections in newborns. Entry of HCMV into cells requires the conserved glycoprotein B (gB), thought to function as a fusogen and reported to bind signaling receptors. gB also elicits a strong immune response in humans and induces the production of neutralizing antibodies although most anti-gB Abs are non-neutralizing. Here, we report the crystal structure of the HCMV gB ectodomain determined to 3.6-A resolution, which is the first atomic-level structure of any betaherpesvirus glycoprotein. The structure of HCMV gB resembles the postfusion structures of HSV-1 and EBV homologs, establishing it as a new member of the class III viral fusogens. Despite structural similarities, each gB has a unique domain arrangement, demonstrating structural plasticity of gB that may accommodate virus-specific functional requirements. The structure illustrates how extensive glycosylation of the gB ectodomain influences antibody recognition. Antigenic sites that elicit neutralizing antibodies are more heavily glycosylated than those that elicit non-neutralizing antibodies, which suggest that HCMV gB uses glycans to shield neutralizing epitopes while exposing non-neutralizing epitopes. This glycosylation pattern may have evolved to direct the immune response towards generation of non-neutralizing antibodies thus helping HCMV to avoid clearance. HCMV gB structure provides a starting point for elucidation of its antigenic and immunogenic properties and aid in the design of recombinant vaccines and monoclonal antibody therapies.

Crystal Structure of the Human Cytomegalovirus Glycoprotein B.,Burke HG, Heldwein EE PLoS Pathog. 2015 Oct 20;11(10):e1005227. doi: 10.1371/journal.ppat.1005227., eCollection 2015 Oct. PMID:26484870^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Halary F, Amara A, Lortat-Jacob H, Messerle M, Delaunay T, Houles C, Fieschi F, Arenzana-Seisdedos F, Moreau JF, Dechanet-Merville J. Human cytomegalovirus binding to DC-SIGN is required for dendritic cell infection and target cell trans-infection. Immunity. 2002 Nov;17(5):653-64. PMID:12433371
↑ Isaacson MK, Compton T. Human cytomegalovirus glycoprotein B is required for virus entry and cell-to-cell spread but not for virion attachment, assembly, or egress. J Virol. 2009 Apr;83(8):3891-903. doi: 10.1128/JVI.01251-08. Epub 2009 Feb 4. PMID:19193805 doi:http://dx.doi.org/10.1128/JVI.01251-08
↑ Burke HG, Heldwein EE. Crystal Structure of the Human Cytomegalovirus Glycoprotein B. PLoS Pathog. 2015 Oct 20;11(10):e1005227. doi: 10.1371/journal.ppat.1005227., eCollection 2015 Oct. PMID:26484870 doi:http://dx.doi.org/10.1371/journal.ppat.1005227

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5cxf"

Categories: Human herpesvirus 5 strain AD169 | Large Structures | Burke HG | Heldwein EE

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5cxf is ON HOLD
+==Crystal structure of the extracellular domain of glycoprotein B from Human Cytomegalovirus==
+<StructureSection load='5cxf' size='340' side='right'caption='[[5cxf]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5cxf]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_herpesvirus_5_strain_AD169 Human herpesvirus 5 strain AD169]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CXF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CXF FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.602&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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'>[https://proteopedia.org/fgij/fg.htm?mol=5cxf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cxf OCA], [https://pdbe.org/5cxf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cxf RCSB], [https://www.ebi.ac.uk/pdbsum/5cxf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cxf ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/GB_HCMVA GB_HCMVA] 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.<ref>PMID:12433371</ref> <ref>PMID:19193805</ref>   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 (By similarity).
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Human cytomegalovirus (HCMV), a dsDNA, enveloped virus, is a ubiquitous pathogen that establishes lifelong latent infections and caused disease in persons with compromised immune systems, e.g., organ transplant recipients or AIDS patients. HCMV is also a leading cause of congenital viral infections in newborns. Entry of HCMV into cells requires the conserved glycoprotein B (gB), thought to function as a fusogen and reported to bind signaling receptors. gB also elicits a strong immune response in humans and induces the production of neutralizing antibodies although most anti-gB Abs are non-neutralizing. Here, we report the crystal structure of the HCMV gB ectodomain determined to 3.6-A resolution, which is the first atomic-level structure of any betaherpesvirus glycoprotein. The structure of HCMV gB resembles the postfusion structures of HSV-1 and EBV homologs, establishing it as a new member of the class III viral fusogens. Despite structural similarities, each gB has a unique domain arrangement, demonstrating structural plasticity of gB that may accommodate virus-specific functional requirements. The structure illustrates how extensive glycosylation of the gB ectodomain influences antibody recognition. Antigenic sites that elicit neutralizing antibodies are more heavily glycosylated than those that elicit non-neutralizing antibodies, which suggest that HCMV gB uses glycans to shield neutralizing epitopes while exposing non-neutralizing epitopes. This glycosylation pattern may have evolved to direct the immune response towards generation of non-neutralizing antibodies thus helping HCMV to avoid clearance. HCMV gB structure provides a starting point for elucidation of its antigenic and immunogenic properties and aid in the design of recombinant vaccines and monoclonal antibody therapies.
-Authors: Burke, H., Heldwein, E.E.
+Crystal Structure of the Human Cytomegalovirus Glycoprotein B.,Burke HG, Heldwein EE PLoS Pathog. 2015 Oct 20;11(10):e1005227. doi: 10.1371/journal.ppat.1005227., eCollection 2015 Oct. PMID:26484870<ref>PMID:26484870</ref>
-Description: Crystal structure of the glycoprotein B ectodomain from Human Cytomegalovirus
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Burke, H]]
+<div class="pdbe-citations 5cxf" style="background-color:#fffaf0;"></div>
-[[Category: Heldwein, E.E]]
+==See Also==
+*[[Glycoproteins B and D|Glycoproteins B and D]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Human herpesvirus 5 strain AD169]]
+[[Category: Large Structures]]
+[[Category: Burke HG]]
+[[Category: Heldwein EE]]

5cxf

From Proteopedia

Current revision

Crystal structure of the extracellular domain of glycoprotein B from Human Cytomegalovirus

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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