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[[Image:1ztx.gif|left|200px]]
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{{STRUCTURE_1ztx|  PDB=1ztx  |  SCENE=  }}
'''West Nile Virus Envelope Protein DIII in complex with neutralizing E16 antibody Fab'''


==West Nile Virus Envelope Protein DIII in complex with neutralizing E16 antibody Fab==
<StructureSection load='1ztx' size='340' side='right'caption='[[1ztx]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1ztx]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/West_Nile_virus West Nile virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZTX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZTX 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]] 2.5&#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=1ztx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ztx OCA], [https://pdbe.org/1ztx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ztx RCSB], [https://www.ebi.ac.uk/pdbsum/1ztx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ztx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q91KZ4_WNV Q91KZ4_WNV]
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zt/1ztx_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ztx ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
West Nile virus is a mosquito-borne flavivirus closely related to the human epidemic-causing dengue, yellow fever and Japanese encephalitis viruses. In establishing infection these icosahedral viruses undergo endosomal membrane fusion catalysed by envelope glycoprotein rearrangement of the putative receptor-binding domain III (DIII) and exposure of the hydrophobic fusion loop. Humoral immunity has an essential protective function early in the course of West Nile virus infection. Here, we investigate the mechanism of neutralization by the E16 monoclonal antibody that specifically binds DIII. Structurally, the E16 antibody Fab fragment engages 16 residues positioned on four loops of DIII, a consensus neutralizing epitope sequence conserved in West Nile virus and distinct in other flaviviruses. The E16 epitope protrudes from the surface of mature virions in three distinct environments, and docking studies predict Fab binding will leave five-fold clustered epitopes exposed. We also show that E16 inhibits infection primarily at a step after viral attachment, potentially by blocking envelope glycoprotein conformational changes. Collectively, our results suggest that a vaccine strategy targeting the dominant DIII epitope may elicit safe and effective immune responses against flaviviral diseases.


==Overview==
Structural basis of West Nile virus neutralization by a therapeutic antibody.,Nybakken GE, Oliphant T, Johnson S, Burke S, Diamond MS, Fremont DH Nature. 2005 Sep 29;437(7059):764-9. PMID:16193056<ref>PMID:16193056</ref>
West Nile virus is a mosquito-borne flavivirus closely related to the human epidemic-causing dengue, yellow fever and Japanese encephalitis viruses. In establishing infection these icosahedral viruses undergo endosomal membrane fusion catalysed by envelope glycoprotein rearrangement of the putative receptor-binding domain III (DIII) and exposure of the hydrophobic fusion loop. Humoral immunity has an essential protective function early in the course of West Nile virus infection. Here, we investigate the mechanism of neutralization by the E16 monoclonal antibody that specifically binds DIII. Structurally, the E16 antibody Fab fragment engages 16 residues positioned on four loops of DIII, a consensus neutralizing epitope sequence conserved in West Nile virus and distinct in other flaviviruses. The E16 epitope protrudes from the surface of mature virions in three distinct environments, and docking studies predict Fab binding will leave five-fold clustered epitopes exposed. We also show that E16 inhibits infection primarily at a step after viral attachment, potentially by blocking envelope glycoprotein conformational changes. Collectively, our results suggest that a vaccine strategy targeting the dominant DIII epitope may elicit safe and effective immune responses against flaviviral diseases.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1ZTX is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [http://en.wikipedia.org/wiki/West_nile_virus West nile virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZTX OCA].
</div>
<div class="pdbe-citations 1ztx" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Structural basis of West Nile virus neutralization by a therapeutic antibody., Nybakken GE, Oliphant T, Johnson S, Burke S, Diamond MS, Fremont DH, Nature. 2005 Sep 29;437(7059):764-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16193056 16193056]
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Single protein]]
[[Category: West Nile virus]]
[[Category: West nile virus]]
[[Category: Diamond MS]]
[[Category: Diamond, M S.]]
[[Category: Fremont DH]]
[[Category: Fremont, D H.]]
[[Category: Nybakken GE]]
[[Category: Nybakken, G E.]]
[[Category: Oliphant T]]
[[Category: Oliphant, T.]]
[[Category: Antibody]]
[[Category: Envelope]]
[[Category: Fab]]
[[Category: Neutralizing]]
[[Category: Virus]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 18:04:19 2008''