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5w0k

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Revision as of 10:25, 8 November 2017

Crystal structure of EBV gHgL/CL40/gp42 N-domain

Structural highlights

5w0k is a 10 chain structure with sequence from Ebvb9 and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	gH, BXLF2 (EBVB9), gL, BKRF2 (EBVB9)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[GH_EBVB9] The heterodimer glycoprotein H-glycoprotein L is required for the fusion of viral and plasma 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. Fusion of EBV with B-lymphocytes requires the additional receptor-binding protein gp42, which forms a complex with gH/gL. May also be required for virus attachment to epithelial cells.^[1] [GL_EBVB9] The heterodimer glycoprotein H-glycoprotein L is required for the fusion of viral and plasma 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. Fusion of EBV with B-lymphocytes requires the additional receptor-binding protein gp42, which forms a complex with gH/gL. May also be required for virus attachment to epithelial cells (By similarity). [GP42_EBVB9] Plays a role in virion attachment to host B-lymphocytes, through binding to leukocyte antigen (HLA) class II and subsequently participates in fusion of the virion with host membranes. May act as a tropism switch that directs fusion with B-lymphocytes and inhibits fusion with epithelial cells.^[2]

Publication Abstract from PubMed

Herpesvirus entry into cells requires the coordinated action of multiple virus envelope glycoproteins, including gH, gL, and gB. For EBV, the gp42 protein assembles into complexes with gHgL heterodimers and binds HLA class II to activate gB-mediated membrane fusion with B cells. EBV tropism is dictated by gp42 levels in the virion, as it inhibits entry into epithelial cells while promoting entry into B cells. The gHgL and gB proteins are targets of neutralizing antibodies and potential candidates for subunit vaccine development, but our understanding of their neutralizing epitopes and the mechanisms of inhibition remain relatively unexplored. Here we studied the structures and mechanisms of two anti-gHgL antibodies, CL40 and CL59, that block membrane fusion with both B cells and epithelial cells. We determined the structures of the CL40 and CL59 complexes with gHgL using X-ray crystallography and EM to identify their epitope locations. CL59 binds to the C-terminal domain IV of gH, while CL40 binds to a site occupied by the gp42 receptor binding domain. CL40 binding to gHgL/gp42 complexes is not blocked by gp42 and does not interfere with gp42 binding to HLA class II, indicating that its ability to block membrane fusion with B cells represents a defect in gB activation. These data indicate that anti-gHgL neutralizing antibodies can block gHgL-mediated activation of gB through different surface epitopes and mechanisms.

Inhibition of EBV-mediated membrane fusion by anti-gHgL antibodies.,Sathiyamoorthy K, Jiang J, Mohl BS, Chen J, Zhou ZH, Longnecker R, Jardetzky TS Proc Natl Acad Sci U S A. 2017 Sep 22. pii: 201704661. doi:, 10.1073/pnas.1704661114. PMID:28939750^[3]

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

References

↑ Oda T, Imai S, Chiba S, Takada K. Epstein-Barr virus lacking glycoprotein gp85 cannot infect B cells and epithelial cells. Virology. 2000 Oct 10;276(1):52-8. PMID:11021994 doi:http://dx.doi.org/10.1006/viro.2000.0531
↑ Borza CM, Hutt-Fletcher LM. Alternate replication in B cells and epithelial cells switches tropism of Epstein-Barr virus. Nat Med. 2002 Jun;8(6):594-9. PMID:12042810 doi:10.1038/nm0602-594
↑ Sathiyamoorthy K, Jiang J, Mohl BS, Chen J, Zhou ZH, Longnecker R, Jardetzky TS. Inhibition of EBV-mediated membrane fusion by anti-gHgL antibodies. Proc Natl Acad Sci U S A. 2017 Sep 22. pii: 201704661. doi:, 10.1073/pnas.1704661114. PMID:28939750 doi:http://dx.doi.org/10.1073/pnas.1704661114

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5w0k"

@@ Line 3: / Line 3: @@
 <StructureSection load='5w0k' size='340' side='right' caption='[[5w0k]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5w0k]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W0K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W0K FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5w0k]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Ebvb9 Ebvb9] 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=5W0K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W0K FirstGlance]. <br>
-</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=5w0k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w0k OCA], [http://pdbe.org/5w0k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w0k RCSB], [http://www.ebi.ac.uk/pdbsum/5w0k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w0k ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gH, BXLF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10377 EBVB9]), gL, BKRF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10377 EBVB9])</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=5w0k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w0k OCA], [http://pdbe.org/5w0k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w0k RCSB], [http://www.ebi.ac.uk/pdbsum/5w0k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w0k ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 21: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Ebvb9]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Jardetzky, T S]]
 [[Category: Sathiyamoorthy, K]]

5w0k

From Proteopedia

Revision as of 10:25, 8 November 2017

Crystal structure of EBV gHgL/CL40/gp42 N-domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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