6cmi: Difference between revisions
New page: '''Unreleased structure''' The entry 6cmi is ON HOLD Authors: Xu, K., Nikolov, D. Description: Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-R... |
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The entry | ==Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody m102.3== | ||
<StructureSection load='6cmi' size='340' side='right'caption='[[6cmi]], [[Resolution|resolution]] 2.72Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6cmi]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Hendra_virus_horse/Australia/Hendra/1994 Hendra virus horse/Australia/Hendra/1994] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CMI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CMI 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]] 2.72Å</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=FUC:ALPHA-L-FUCOSE'>FUC</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=6cmi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cmi OCA], [https://pdbe.org/6cmi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cmi RCSB], [https://www.ebi.ac.uk/pdbsum/6cmi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cmi ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/GLYCP_HENDH GLYCP_HENDH] Attaches the virus to sialic acid-containing cell receptors and thereby initiating infection. Binding of glycoprotein G to the receptor induces a conformational change that allows the F protein to trigger virion/cell membranes fusion (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The henipaviruses, represented by Hendra (HeV) and Nipah (NiV) viruses are highly pathogenic zoonotic paramyxoviruses with uniquely broad host tropisms responsible for repeated outbreaks in Australia, Southeast Asia, India and Bangladesh. The high morbidity and mortality rates associated with infection and lack of licensed antiviral therapies make the henipaviruses a potential biological threat to humans and livestock. Henipavirus entry is initiated by the attachment of the G envelope glycoprotein to host cell membrane receptors. Previously, henipavirus-neutralizing human monoclonal antibodies (hmAb) have been isolated using the HeV-G glycoprotein and a human naive antibody library. One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection, has been used in several people on a compassionate use basis, and is currently in development for use in humans. Here, we report the crystal structure of the complex of HeV-G with m102.3, an m102.4 derivative, and describe NiV and HeV escape mutants. This structure provides detailed insight into the mechanism of HeV and NiV neutralization by m102.4, and serves as a blueprint for further optimization of m102.4 as a therapeutic agent and for the development of entry inhibitors and vaccines. | |||
Crystal structure of the Hendra virus attachment G glycoprotein bound to a potent cross-reactive neutralizing human monoclonal antibody.,Xu K, Rockx B, Xie Y, DeBuysscher BL, Fusco DL, Zhu Z, Chan YP, Xu Y, Luu T, Cer RZ, Feldmann H, Mokashi V, Dimitrov DS, Bishop-Lilly KA, Broder CC, Nikolov DB PLoS Pathog. 2013;9(10):e1003684. doi: 10.1371/journal.ppat.1003684. Epub 2013, Oct 10. PMID:24130486<ref>PMID:24130486</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Nikolov | <div class="pdbe-citations 6cmi" style="background-color:#fffaf0;"></div> | ||
[[Category: Xu | |||
==See Also== | |||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Hendra virus horse/Australia/Hendra/1994]] | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Nikolov D]] | |||
[[Category: Xu K]] | |||
Latest revision as of 10:52, 17 October 2024
Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody m102.3Crystal Structure of the Hendra Virus Attachment G Glycoprotein Bound to a Potent Cross-Reactive Neutralizing Human Monoclonal Antibody m102.3
Structural highlights
FunctionGLYCP_HENDH Attaches the virus to sialic acid-containing cell receptors and thereby initiating infection. Binding of glycoprotein G to the receptor induces a conformational change that allows the F protein to trigger virion/cell membranes fusion (By similarity). Publication Abstract from PubMedThe henipaviruses, represented by Hendra (HeV) and Nipah (NiV) viruses are highly pathogenic zoonotic paramyxoviruses with uniquely broad host tropisms responsible for repeated outbreaks in Australia, Southeast Asia, India and Bangladesh. The high morbidity and mortality rates associated with infection and lack of licensed antiviral therapies make the henipaviruses a potential biological threat to humans and livestock. Henipavirus entry is initiated by the attachment of the G envelope glycoprotein to host cell membrane receptors. Previously, henipavirus-neutralizing human monoclonal antibodies (hmAb) have been isolated using the HeV-G glycoprotein and a human naive antibody library. One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection, has been used in several people on a compassionate use basis, and is currently in development for use in humans. Here, we report the crystal structure of the complex of HeV-G with m102.3, an m102.4 derivative, and describe NiV and HeV escape mutants. This structure provides detailed insight into the mechanism of HeV and NiV neutralization by m102.4, and serves as a blueprint for further optimization of m102.4 as a therapeutic agent and for the development of entry inhibitors and vaccines. Crystal structure of the Hendra virus attachment G glycoprotein bound to a potent cross-reactive neutralizing human monoclonal antibody.,Xu K, Rockx B, Xie Y, DeBuysscher BL, Fusco DL, Zhu Z, Chan YP, Xu Y, Luu T, Cer RZ, Feldmann H, Mokashi V, Dimitrov DS, Bishop-Lilly KA, Broder CC, Nikolov DB PLoS Pathog. 2013;9(10):e1003684. doi: 10.1371/journal.ppat.1003684. Epub 2013, Oct 10. PMID:24130486[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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