7x2w
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7x2w]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Coxsackievirus_B1 Coxsackievirus B1] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7X2W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7X2W FirstGlance]. <br> | <table><tr><td colspan='2'>[[7x2w]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Coxsackievirus_B1 Coxsackievirus B1] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7X2W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7X2W FirstGlance]. <br> | ||
| - | </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=7x2w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7x2w OCA], [https://pdbe.org/7x2w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7x2w RCSB], [https://www.ebi.ac.uk/pdbsum/7x2w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7x2w ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.24Å</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=7x2w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7x2w OCA], [https://pdbe.org/7x2w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7x2w RCSB], [https://www.ebi.ac.uk/pdbsum/7x2w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7x2w ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| - | == Function == | ||
| - | [[https://www.uniprot.org/uniprot/W8GTF7_9ENTO W8GTF7_9ENTO]] | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Coxsackievirus B1 (CVB1) is an emerging pathogen associated with severe neonatal diseases including aseptic meningitis, myocarditis, and pancreatitis and also with the development of type 1 diabetes. We characterize the binding and therapeutic efficacies of three CVB1-specific neutralizing antibodies (nAbs) identified for their ability to inhibit host receptor engagement. High-resolution cryo-EM structures showed that these antibodies recognize different epitopes but with an overlapping region in the capsid VP2 protein and specifically the highly variable EF loop. Moreover, they perturb capsid-receptor interactions by binding various viral particle forms. Antibody combinations achieve synergetic neutralization via a stepwise capsid transition and virion disruption, indicating dynamic changes in the virion in response to multiple nAbs targeting the receptor-binding site. Furthermore, this three-antibody cocktail protects against lethal challenge in neonatal mice and limits pancreatitis and viral replication in a non-obese diabetic mouse model. These results illustrate the utility of nAbs for rational design of therapeutics against picornaviruses such as CVB. | Coxsackievirus B1 (CVB1) is an emerging pathogen associated with severe neonatal diseases including aseptic meningitis, myocarditis, and pancreatitis and also with the development of type 1 diabetes. We characterize the binding and therapeutic efficacies of three CVB1-specific neutralizing antibodies (nAbs) identified for their ability to inhibit host receptor engagement. High-resolution cryo-EM structures showed that these antibodies recognize different epitopes but with an overlapping region in the capsid VP2 protein and specifically the highly variable EF loop. Moreover, they perturb capsid-receptor interactions by binding various viral particle forms. Antibody combinations achieve synergetic neutralization via a stepwise capsid transition and virion disruption, indicating dynamic changes in the virion in response to multiple nAbs targeting the receptor-binding site. Furthermore, this three-antibody cocktail protects against lethal challenge in neonatal mice and limits pancreatitis and viral replication in a non-obese diabetic mouse model. These results illustrate the utility of nAbs for rational design of therapeutics against picornaviruses such as CVB. | ||
| - | Structural basis for the synergistic neutralization of coxsackievirus B1 by a triple-antibody cocktail.,Zheng Q, Zhu R, Yin Z, Xu L, Sun H, Yu H, Wu Y, Jiang Y, Huang Q, Huang Y, Zhang D, Liu L, Yang H, He M, Zhou Z, Jiang Y, Chen Z, Zhao H, Que Y, Kong Z, Zhou L, Li T, Zhang J, Luo W, Gu Y, Cheng T, Li S, Xia N Cell Host Microbe. 2022 Sep 14;30(9):1279-1294.e6. doi:, 10.1016/j.chom.2022.08.001. Epub 2022 Aug 23. PMID:36002016<ref>PMID:36002016</ref> | + | Structural basis for the synergistic neutralization of coxsackievirus B1 by a triple-antibody cocktail.,Zheng Q, Zhu R, Yin Z, Xu L, Sun H, Yu H, Wu Y, Jiang Y, Huang Q, Huang Y, Zhang D, Liu L, Yang H, He M, Zhou Z, Jiang Y, Chen Z, Zhao H, Que Y, Kong Z, Zhou L, Li T, Zhang J, Luo W, Gu Y, Cheng T, Li S, Xia N Cell Host Microbe. 2022 Sep 14;30(9):1279-1294.e6. doi: , 10.1016/j.chom.2022.08.001. Epub 2022 Aug 23. PMID:36002016<ref>PMID:36002016</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
Cryo-EM structure of Coxsackievirus B1 pre-A particle in complex with nAb 8A10 (CVB1-pre-A:8A10)
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Categories: Coxsackievirus B1 | Large Structures | Mus musculus | Cheng T | Li S | Sun H | Xia N | Zheng Q | Zhu R
