6iek

From Proteopedia

(Difference between revisions)

Current revision

Structure of RVFV Gn and human monoclonal antibody R12

Structural highlights

6iek is a 6 chain structure with sequence from Homo sapiens and Rift Valley fever virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.7Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GP_RVFV Structural component of the virion that interacts with glycoprotein C (By similarity). It shields the hydrophobic fusion loops of the glycoprotein C, preventing premature fusion (By similarity). The glycoprotein protrusions are arranged on an icosahedral lattice, with T=12 triangulation (PubMed:19193794, PubMed:23319635). They are able to attach the virion to the host cell receptor CD209/DC-SIGN and to promote fusion of membranes with the late endosome after endocytosis of the virion (By similarity). Plays a role in the packaging of ribonucleoproteins and polymerase during virus assembly (By similarity).[UniProtKB:P09613][UniProtKB:P21401]^[1] ^[2] Structural component of the virion that interacts with glycoprotein N (By similarity). Acts as a class II fusion protein that is activated upon acidification and subsequent repositioning of the glycoprotein N (PubMed:23319635, PubMed:29097548). The glycoprotein protrusions are arranged on an icosahedral lattice, with T=12 triangulation (PubMed:19193794, PubMed:23319635). They are able to attach the virion to the host cell receptor CD209/DC-SIGN and to promote fusion of membranes with the late endosome after endocytosis of the virion (By similarity).[UniProtKB:P09613]^[3] ^[4] ^[5] Plays a role for virus dissemination in the mosquito.[UniProtKB:P21401]^[6] Plays a role for virus dissemination in mosquitoes.[UniProtKB:P21401]

Publication Abstract from PubMed

Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that causes substantial morbidity and mortality in livestock and humans. To date, there are no licensed human vaccines or therapeutics available. Here, we report the isolation of monoclonal antibodies from a convalescent patient, targeting the RVFV envelope proteins Gn and Gc. The Gn-specific monoclonal antibodies exhibited much higher neutralizing activities in vitro and protection efficacies in mice against RVFV infection, compared to the Gc-specific monoclonal antibodies. The Gn monoclonal antibodies were found to interfere with soluble Gn binding to cells and prevent infection by blocking the attachment of virions to host cells. Structural analysis of Gn complexed with four Gn-specific monoclonal antibodies resulted in the definition of three antigenic patches (A, B and C) on Gn domain I. Both patches A and B are major neutralizing epitopes. Our results highlight the potential of antibody-based therapeutics and provide a structure-based rationale for designing vaccines against RVFV.

Neutralization mechanism of human monoclonal antibodies against Rift Valley fever virus.,Wang Q, Ma T, Wu Y, Chen Z, Zeng H, Tong Z, Gao F, Qi J, Zhao Z, Chai Y, Yang H, Wong G, Bi Y, Wu L, Shi R, Yang M, Song J, Jiang H, An Z, Wang J, Yilma TD, Shi Y, Liu WJ, Liang M, Qin C, Gao GF, Yan J Nat Microbiol. 2019 Apr 1. pii: 10.1038/s41564-019-0411-z. doi:, 10.1038/s41564-019-0411-z. PMID:30936489^[7]

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

References

↑ Huiskonen JT, Overby AK, Weber F, Grunewald K. Electron cryo-microscopy and single-particle averaging of Rift Valley fever virus: evidence for GN-GC glycoprotein heterodimers. J Virol. 2009 Apr;83(8):3762-9. doi: 10.1128/JVI.02483-08. Epub 2009 Feb 4. PMID:19193794 doi:http://dx.doi.org/10.1128/JVI.02483-08
↑ Dessau M, Modis Y. Crystal structure of glycoprotein C from Rift Valley fever virus. Proc Natl Acad Sci U S A. 2013 Jan 14. PMID:23319635 doi:http://dx.doi.org/10.1073/pnas.1217780110
↑ Huiskonen JT, Overby AK, Weber F, Grunewald K. Electron cryo-microscopy and single-particle averaging of Rift Valley fever virus: evidence for GN-GC glycoprotein heterodimers. J Virol. 2009 Apr;83(8):3762-9. doi: 10.1128/JVI.02483-08. Epub 2009 Feb 4. PMID:19193794 doi:http://dx.doi.org/10.1128/JVI.02483-08
↑ Dessau M, Modis Y. Crystal structure of glycoprotein C from Rift Valley fever virus. Proc Natl Acad Sci U S A. 2013 Jan 14. PMID:23319635 doi:http://dx.doi.org/10.1073/pnas.1217780110
↑ Guardado-Calvo P, Atkovska K, Jeffers SA, Grau N, Backovic M, Perez-Vargas J, de Boer SM, Tortorici MA, Pehau-Arnaudet G, Lepault J, England P, Rottier PJ, Bosch BJ, Hub JS, Rey FA. A glycerophospholipid-specific pocket in the RVFV class II fusion protein drives target membrane insertion. Science. 2017 Nov 3;358(6363):663-667. doi: 10.1126/science.aal2712. PMID:29097548 doi:http://dx.doi.org/10.1126/science.aal2712
↑ Kading RC, Crabtree MB, Bird BH, Nichol ST, Erickson BR, Horiuchi K, Biggerstaff BJ, Miller BR. Deletion of the NSm virulence gene of Rift Valley fever virus inhibits virus replication in and dissemination from the midgut of Aedes aegypti mosquitoes. PLoS Negl Trop Dis. 2014 Feb 13;8(2):e2670. doi: 10.1371/journal.pntd.0002670., eCollection 2014 Feb. PMID:24551252 doi:http://dx.doi.org/10.1371/journal.pntd.0002670
↑ Wang Q, Ma T, Wu Y, Chen Z, Zeng H, Tong Z, Gao F, Qi J, Zhao Z, Chai Y, Yang H, Wong G, Bi Y, Wu L, Shi R, Yang M, Song J, Jiang H, An Z, Wang J, Yilma TD, Shi Y, Liu WJ, Liang M, Qin C, Gao GF, Yan J. Neutralization mechanism of human monoclonal antibodies against Rift Valley fever virus. Nat Microbiol. 2019 Apr 1. pii: 10.1038/s41564-019-0411-z. doi:, 10.1038/s41564-019-0411-z. PMID:30936489 doi:http://dx.doi.org/10.1038/s41564-019-0411-z

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/6iek"

@@ Line 3: / Line 3: @@
 <StructureSection load='6iek' size='340' side='right'caption='[[6iek]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6iek]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Rvfv Rvfv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IEK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IEK FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6iek]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rift_Valley_fever_virus Rift Valley fever virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IEK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6IEK 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=6iek FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6iek OCA], [http://pdbe.org/6iek PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6iek RCSB], [http://www.ebi.ac.uk/pdbsum/6iek PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6iek ProSAT]</span></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]] 2.7&#8491;</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=6iek FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6iek OCA], [https://pdbe.org/6iek PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6iek RCSB], [https://www.ebi.ac.uk/pdbsum/6iek PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6iek ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/GP_RVFV GP_RVFV] Structural component of the virion that interacts with glycoprotein C (By similarity). It shields the hydrophobic fusion loops of the glycoprotein C, preventing premature fusion (By similarity). The glycoprotein protrusions are arranged on an icosahedral lattice, with T=12 triangulation (PubMed:19193794, PubMed:23319635). They are able to attach the virion to the host cell receptor CD209/DC-SIGN and to promote fusion of membranes with the late endosome after endocytosis of the virion (By similarity). Plays a role in the packaging of ribonucleoproteins and polymerase during virus assembly (By similarity).[UniProtKB:P09613][UniProtKB:P21401]<ref>PMID:19193794</ref> <ref>PMID:23319635</ref>   Structural component of the virion that interacts with glycoprotein N (By similarity). Acts as a class II fusion protein that is activated upon acidification and subsequent repositioning of the glycoprotein N (PubMed:23319635, PubMed:29097548). The glycoprotein protrusions are arranged on an icosahedral lattice, with T=12 triangulation (PubMed:19193794, PubMed:23319635). They are able to attach the virion to the host cell receptor CD209/DC-SIGN and to promote fusion of membranes with the late endosome after endocytosis of the virion (By similarity).[UniProtKB:P09613]<ref>PMID:19193794</ref> <ref>PMID:23319635</ref> <ref>PMID:29097548</ref>   Plays a role for virus dissemination in the mosquito.[UniProtKB:P21401]<ref>PMID:24551252</ref>   Plays a role for virus dissemination in mosquitoes.[UniProtKB:P21401]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 15: / Line 18: @@
 </div>
 <div class="pdbe-citations 6iek" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Rvfv]]
+[[Category: Rift Valley fever virus]]
-[[Category: Gao, F]]
+[[Category: Gao F]]
-[[Category: Gao, G F]]
+[[Category: Gao GF]]
-[[Category: Qi, J X]]
+[[Category: Qi JX]]
-[[Category: Wang, Q H]]
+[[Category: Wang QH]]
-[[Category: Wu, Y]]
+[[Category: Wu Y]]
-[[Category: Antibody]]
-[[Category: Structural protein]]
-[[Category: Structural protein-immune system complex]]

6iek

From Proteopedia

Current revision

Structure of RVFV Gn and human monoclonal antibody R12

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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