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| | <SX load='6gv4' size='340' side='right' viewer='molstar' caption='[[6gv4]], [[Resolution|resolution]] 2.80Å' scene=''> | | <SX load='6gv4' size='340' side='right' viewer='molstar' caption='[[6gv4]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6gv4]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Human_parechovirus_3 Human parechovirus 3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GV4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6GV4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6gv4]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_parechovirus_3 Human parechovirus 3]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GV4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6GV4 FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6gv4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gv4 OCA], [http://pdbe.org/6gv4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gv4 RCSB], [http://www.ebi.ac.uk/pdbsum/6gv4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gv4 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]] 2.8Å</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=6gv4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gv4 OCA], [https://pdbe.org/6gv4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6gv4 RCSB], [https://www.ebi.ac.uk/pdbsum/6gv4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6gv4 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q8BES5_9PICO Q8BES5_9PICO] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Human parechovirus 3]] | | [[Category: Human parechovirus 3]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Butcher, S J]] | + | [[Category: Butcher SJ]] |
| - | [[Category: Domanska, A]] | + | [[Category: Domanska A]] |
| - | [[Category: Flatt, J W]] | + | [[Category: Flatt JW]] |
| - | [[Category: Geraets, J A]] | + | [[Category: Geraets JA]] |
| - | [[Category: Jukonen, J J.J]] | + | [[Category: Jukonen JJJ]] |
| - | [[Category: Antibody]]
| + | |
| - | [[Category: Human parechovirus]]
| + | |
| - | [[Category: Rna]]
| + | |
| - | [[Category: Virus]]
| + | |
| Structural highlights
Function
Q8BES5_9PICO
Publication Abstract from PubMed
Human parechovirus 3 (HPeV3) infection is associated with sepsis in neonates characterized by significant immune activation and subsequent tissue damage. Strategies to limit infection have been unsuccessful due to inadequate molecular diagnostic tools for early detection and lack of a vaccine or specific antiviral therapy. Towards the latter, we present a 2.8 A-resolution structure of HPeV3 in complex with fragments from a neutralizing human monoclonal antibody AT12-015 using cryo-EM and image reconstruction. Modeling revealed that the epitope extends across neighboring asymmetric units with contributions from capsid proteins VP0, VP1, and VP3. Antibody decoration was found to block binding of HPeV3 to cultured cells. Additionally at high-resolution, it was possible to model a stretch of RNA inside the virion and from this identify the key features that drive and stabilize protein-RNA association during assembly.IMPORTANCE HPeV3 is receiving increasing attention as a prevalent cause of sepsis-like symptoms in neonates, which despite the severity of disease, there are no effective treatments available. Structural and molecular insights into virus neutralization are urgently needed, especially as clinical cases are on the rise. Towards this goal, we present the first structure of HPeV3 in complex with fragments from a neutralizing monoclonal antibody. At high-resolution it was possible to precisely define the epitope that when targeted, prevents virions from binding to cells. Such an atomic-level description is useful for understanding host-pathogen interaction, viral pathogenesis mechanisms, and for finding potential cures for infection and disease.
2.8 A resolution cryo-EM structure of human parechovirus 3 in complex with Fab from a neutralizing antibody.,Domanska A, Flatt JW, Jukonen JJJ, Geraets JA, Butcher SJ J Virol. 2018 Nov 21. pii: JVI.01597-18. doi: 10.1128/JVI.01597-18. PMID:30463974[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Domanska A, Flatt JW, Jukonen JJJ, Geraets JA, Butcher SJ. 2.8 A resolution cryo-EM structure of human parechovirus 3 in complex with Fab from a neutralizing antibody. J Virol. 2018 Nov 21. pii: JVI.01597-18. doi: 10.1128/JVI.01597-18. PMID:30463974 doi:http://dx.doi.org/10.1128/JVI.01597-18
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