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| | <SX load='3j7e' size='340' side='right' viewer='molstar' caption='[[3j7e]], [[Resolution|resolution]] 13.60Å' scene=''> | | <SX load='3j7e' size='340' side='right' viewer='molstar' caption='[[3j7e]], [[Resolution|resolution]] 13.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3j7e]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3J7E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3J7E FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3j7e]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3J7E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3J7E FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3j7g|3j7g]]</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]] 13.6Å</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=3j7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3j7e OCA], [http://pdbe.org/3j7e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3j7e RCSB], [http://www.ebi.ac.uk/pdbsum/3j7e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3j7e ProSAT]</span></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=3j7e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3j7e OCA], [https://pdbe.org/3j7e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3j7e RCSB], [https://www.ebi.ac.uk/pdbsum/3j7e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3j7e ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/K7TH34_MOUSE K7TH34_MOUSE] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: Brendle, S A]] | + | [[Category: Brendle SA]] |
| - | [[Category: Bywaters, S M]] | + | [[Category: Bywaters SM]] |
| - | [[Category: Christensen, N D]] | + | [[Category: Christensen ND]] |
| - | [[Category: Hafenstein, S]] | + | [[Category: Hafenstein S]] |
| - | [[Category: Lee, H]] | + | [[Category: Lee H]] |
| - | [[Category: Hi and fg loop]]
| + | |
| - | [[Category: Hpv16 capsid]]
| + | |
| - | [[Category: Hpv16 v5 fab variable domain]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Maturation]]
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| - | [[Category: Neutralization antibody]]
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| - | [[Category: Virus-fab complex]]
| + | |
| Structural highlights
Function
K7TH34_MOUSE
Publication Abstract from PubMed
Human papillomavirus 16 (HPV16) is a worldwide health threat and an etiologic agent of cervical cancer. To understand the antigenic properties of HPV16 we pursued a structural study to elucidate HPV capsids and antibody interactions. The cryo-EM structures of HPV16 mature and an altered capsid particles were solved individually and as complexes with fragment of antibody (Fab) from the neutralizing antibody H16.V5. Fitted crystal structures provided a pseudo-atomic model of the virus-Fab complex, which identified a precise footprint of H16.V5, including previously unrecognized residues. The altered capsid-Fab complex map showed that binding of the Fab induced significant conformational changes than were seen in the altered capsid structure alone. These changes included more ordered surface loops, consolidated invading arm structures, and tighter inter-capsomeric connections at the capsid floor. The H16.V5 Fab preferentially bound hexavalent capsomers likely with a stabilizing effect that directly correlated with the number of bound Fabs. Additional cryoEM reconstructions of the virus-Fab complex for different incubation times and structural analysis provide a model for a hyper-stabilization of the capsomer by H16.V5 Fab and showed that the Fab distinguishes subtle differences between antigenic sites. IMPORTANCE: Our analysis of the cryoEM reconstructions of the HPV16 capsids and virus-Fab complexes has identified the entire HPV.V5 conformational epitope and demonstrated a detailed neutralization mechanism of this clinically important monoclonal antibody against HPV16. The Fab bound and ordered the apical loops of HPV16. This conformational change was transmitted to the lower region of the capsomer resulting in enhanced inter-capsomeric interactions evidenced by the more ordered capsid floor and 'invading arm' structures. This study advances the understanding of the neutralization mechanism used by H16.V5.
A CryoEM study identifies the complete H16.V5 epitope and reveals global conformational changes initiated by binding of the neutralizing antibody fragment.,Lee H, Brendle SA, Bywaters SM, Guan J, Ashley RE, Yoder JD, Makhov AM, Conway JF, Christensen ND, Hafenstein S J Virol. 2014 Nov 12. pii: JVI.02898-14. PMID:25392224[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lee H, Brendle SA, Bywaters SM, Guan J, Ashley RE, Yoder JD, Makhov AM, Conway JF, Christensen ND, Hafenstein S. A CryoEM study identifies the complete H16.V5 epitope and reveals global conformational changes initiated by binding of the neutralizing antibody fragment. J Virol. 2014 Nov 12. pii: JVI.02898-14. PMID:25392224 doi:http://dx.doi.org/10.1128/JVI.02898-14
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