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==High-Resolution Structure Analysis of Antibody V5 and U4 Conformational Epitope on Human Papillomavirus 16==
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== Structural highlights ==
<table><tr><td colspan='2'>[[6bsp]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_papillomavirus_type_16 Human papillomavirus type 16] 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=6BSP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BSP FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.7&#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=6bsp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bsp OCA], [https://pdbe.org/6bsp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bsp RCSB], [https://www.ebi.ac.uk/pdbsum/6bsp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bsp ProSAT]</span></td></tr>
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== Function ==
[https://www.uniprot.org/uniprot/VL1_HPV16 VL1_HPV16] Forms an icosahedral capsid with a T=7 symmetry and a 50 nm diameter. The capsid is composed of 72 pentamers linked to each other by disulfide bonds and associated with L2 proteins. Binds to heparan sulfate proteoglycans on cell surface of basal layer keratinocytes to provide initial virion attachment. This binding mediates a conformational change in the virus capsid that facilitates efficient infection. The virion enters the host cell via endocytosis. During virus trafficking, L1 protein dissociates from the viral DNA and the genomic DNA is released to the host nucleus. The virion assembly takes place within the cell nucleus. Encapsulates the genomic DNA together with protein L2.[HAMAP-Rule:MF_04002]<ref>PMID:12610160</ref> <ref>PMID:26289843</ref> <ref>PMID:8553535</ref> 
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== Publication Abstract from PubMed ==
Cancers attributable to human papillomavirus (HPV) place a huge burden on the health of both men and women. The current commercial vaccines are genotype specific and provide little therapeutic benefit to patients with existing HPV infections. Identifying the conformational epitopes on the virus capsid supports the development of improved recombinant vaccines to maximize long-term protection against multiple types of HPV. Fragments of antibody (Fab) digested from the neutralizing monoclonal antibodies H16.V5 (V5) and H16.U4 (U4) were bound to HPV16 capsids and the structures of the two virus-Fab complexes were solved to near atomic resolution using cryo-electron microscopy. The structures reveal virus conformational changes, the Fab-binding mode to the capsid, the residues comprising the epitope and indicate a potential interaction of U4 with the minor structural protein, L2. Competition enzyme-linked immunosorbent assay (ELISA) showed V5 outcompetes U4 when added sequentially, demonstrating a steric interference even though the footprints do not overlap. Combined with our previously reported immunological and structural results, we propose that the virus may initiate host entry through an interaction between the icosahedral five-fold vertex of the capsid and receptors on the host cell. The highly detailed epitopes identified for the two antibodies provide a framework for continuing biochemical, genetic and biophysical studies.

High-Resolution Structure Analysis of Antibody V5 and U4 Conformational Epitopes on Human Papillomavirus 16.,Guan J, Bywaters SM, Brendle SA, Ashley RE, Makhov AM, Conway JF, Christensen ND, Hafenstein S Viruses. 2017 Dec 6;9(12). pii: v9120374. doi: 10.3390/v9120374. PMID:29211035<ref>PMID:29211035</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]]
== References ==
<references/>
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[[Category: Human papillomavirus type 16]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Ashley RE]]
[[Category: Brendle SA]]
[[Category: Bywaters SM]]
[[Category: Christenson ND]]
[[Category: Conway JF]]
[[Category: Guan J]]
[[Category: Hafenstein S]]
[[Category: Makhov AM]]