View source for 4x7d


==Crystal structure of 2012 NSW GII.4 P domain in complex with Nano-85==
<StructureSection load='4x7d' size='340' side='right'caption='[[4x7d]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4x7d]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Camelus_glama Camelus glama] and [http://en.wikipedia.org/wiki/Norovirus_hu/gii.4/sydney/nsw0514/2012/au Norovirus hu/gii.4/sydney/nsw0514/2012/au]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X7D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X7D 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></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=4x7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x7d OCA], [http://pdbe.org/4x7d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x7d RCSB], [http://www.ebi.ac.uk/pdbsum/4x7d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4x7d ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
Human noroviruses are icosahedral single-stranded RNA viruses. The capsid protein is divided into shell (S) and protruding (P) domains, which are connected by a flexible hinge region. There are numerous genetically and antigenically distinct noroviruses and the dominant strains evolve every other year. Vaccine and antiviral development is hampered by the difficulties in growing human norovirus in cell culture and the continually evolving strains. Here, we show the X-ray crystal structures of human norovirus P domains in complex with two different Nanobodies. One Nanobody, Nano-85, was broadly reactive, while the other, Nano-25, was strain specific. We showed that both Nanobodies bound to the lower region on the P domain and had nanomolar affinities. The Nano-85 binding site mainly compromised of highly conserved amino acids among the genetically distinct genogroup II noroviruses. Several of the conserved residues were also recognized by a broadly reactive monoclonal antibody, which suggested this region contained a dominant epitope. Superposition of the P domain Nanobody complex structures into a cryo-EM particle structure revealed that both Nanobodies bound at occluded sites on the particles. The flexible hinge region, which contained approximately 10-12 amino acids, likely permitted a certain degree of P domain movement on the particles in order to accommodate the Nanobodies. Interestingly, the Nano-85 binding interaction with intact particles caused the particles to disassemble in vitro. Altogether, these results suggested that the highly conserved Nano-85 binding epitope contained a trigger mechanism for particle disassembly. Principally, this epitope represents a potential site of norovirus vulnerability. IMPORTANCE: We characterized two different Nanobodies (Nano-85 and Nano-25) that bind to human noroviruses. Both Nanobodies bound with high affinities to the lower region of the P domain, which was occluded on intact particles. Nano-25 was specific for GII.10, whereas Nano-85 bound several different GII genotypes, including GII.4, GII.10, and GII.12. We showed that Nano-85 was able to detect norovirus virions in clinical stool specimens using a sandwich ELISA. Importantly, we found that Nano-85 binding to intact particles caused the particles to disassemble. We believe that with further testing, Nano-85 will not only work as a diagnostic reagent in norovirus detection systems, but could also function as a broadly reactive GII norovirus antiviral.

Nanobody binding to a conserved epitope promoted human norovirus particle disassembly.,Koromyslova AD, Hansman GS J Virol. 2014 Dec 17. pii: JVI.03176-14. PMID:25520510<ref>PMID:25520510</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 4x7d" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Camelus glama]]
[[Category: Large Structures]]
[[Category: Norovirus hu/gii 4/sydney/nsw0514/2012/au]]
[[Category: Hansman, G S]]
[[Category: Koromyslova, A D]]
[[Category: Nanobody]]
[[Category: Norovirus]]
[[Category: Protruding domain]]
[[Category: Vhh domain]]
[[Category: Viral protein]]