View source for 5o03


==GII.10 Vietnam 026 protruding domain in complex with Nanobody Nano-32==
<StructureSection load='5o03' size='340' side='right' caption='[[5o03]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5o03]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Norovirus_gii.10 Norovirus gii.10] and [http://en.wikipedia.org/wiki/Norwalk_calicivirus Norwalk calicivirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O03 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O03 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene></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=5o03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o03 OCA], [http://pdbe.org/5o03 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o03 RCSB], [http://www.ebi.ac.uk/pdbsum/5o03 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o03 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Norovirus is the leading cause of gastroenteritis worldwide. Despite recent developments in norovirus propagation in cell culture, these viruses are still challenging to grow routinely. Moreover, little is known on how norovirus infects the host cells, except that histo-blood group antigens (HBGAs) are important binding factors for infection and cell entry. Antibodies that bind at the HBGA pocket and block attachment to HBGAs are believed to neutralize the virus. However, additional neutralization epitopes elsewhere on the capsid likely exist and impeding the intrinsic structural dynamics of the capsid could be equally important. In the current study, we investigated a panel of Nanobodies in order to probe functional epitopes that could trigger capsid rearrangement and/ or interfere with HBGA binding interactions. The precise binding sites of six Nanobodies (Nano-4, Nano-14, Nano-26, Nano-27, Nano-32, and Nano-42) were identified using X-ray crystallography. We showed that these Nanobodies bound on the top, side, and bottom of the norovirus protruding domain. The impact of Nanobody binding on norovirus capsid morphology was analyzed using electron microscopy and dynamic light scattering. We discovered that distinct Nanobody epitopes were associated with varied changes in particle structural integrity and assembly. Interestingly, certain Nanobody-induced capsid morphological changes lead to the capsid protein degradation and viral RNA exposure. Moreover, Nanobodies employed multiple inhibition mechanisms to prevent norovirus attachment to HBGAs, which included steric obstruction (Nano-14), allosteric interference (Nano-32), and violation of normal capsid morphology (Nano-26 and Nano-85). Finally, we showed that two Nanobodies (Nano-26 and Nano-85) not only compromised capsid integrity and inhibited VLPs attachment to HBGAs, but also recognized a broad panel of norovirus genotypes with high affinities. Consequently, Nano-26 and Nano-85 have a great potential to function as novel therapeutic agents against human noroviruses.

Nanobodies targeting norovirus capsid reveal functional epitopes and potential mechanisms of neutralization.,Koromyslova AD, Hansman GS PLoS Pathog. 2017 Nov 2;13(11):e1006636. doi: 10.1371/journal.ppat.1006636., eCollection 2017 Nov. PMID:29095961<ref>PMID:29095961</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5o03" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Norovirus gii 10]]
[[Category: Norwalk calicivirus]]
[[Category: Hansman, G H]]
[[Category: Koromyslova, A D]]
[[Category: Capsid]]
[[Category: Nanobody]]
[[Category: Norovirus]]
[[Category: Protruding domain]]
[[Category: Vhh]]
[[Category: Viral protein]]