4oos

<StructureSection load='4oos' size='340' side='right' caption='[[4oos]], [[Resolution|resolution]] 1.64&Aring;' scene=''>

<table><tr><td colspan='2'>[[4oos]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OOS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OOS 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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4op7|4op7]], [[4opo|4opo]]</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=4oos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oos OCA], [http://pdbe.org/4oos PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4oos RCSB], [http://www.ebi.ac.uk/pdbsum/4oos PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4oos ProSAT]</span></td></tr>

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== Publication Abstract from PubMed ==

Human noroviruses are the dominant cause of outbreaks of gastroenteritis around the world. Human norovirus interacts with the polymorphic human histo-blood group antigens (HBGAs) and this interaction is thought to be important for infection. Indeed, synthetic HBGAs or HBGA-expressing enteric bacteria were shown to enhance norovirus infection in B cells. A number of studies have found a possible relationship between HBGA type and norovirus susceptibility. The genogroup II genotype 4 (GII.4) noroviruses are the dominant cluster, evolve every other year, and are thought to modify their binding interactions to different HBGA types. Here, we show the high-resolution X-ray crystal structures of the capsid protruding (P) domains from epidemic GII.4 variants in 2004, 2006, and 2012, co-crystallized with a panel of HBGA types (H type 2, Lewis Y, Lewis B, Lewis A, Lewis X, A-type, and B-type). Many of the HBGA binding interactions were found to be complex, involving capsid loop movements, alternative HBGA conformations, and HBGA rotations. We showed that a loop (residues 391-395) was elegantly repositioned in order to allow for Lewis Y binding. This loop was also slightly shifted to provide direct hydrogen and water-mediated bonds with Lewis B. We considered that the flexible loop modulated Lewis HBGA binding. The GII.4 noroviruses have dominated outbreaks over the past decade, which may be explained by their exquisite HBGA binding mechanisms, their fondness for Lewis HBGAs, and their temporal amino acid modifications. IMPORTANCE: Our data provides a comprehensive picture of GII.4 P domain and HBGA binding interactions. The exceptionally high resolutions of our X-ray crystal structures allowed us to accurately recognize novel GII.4 P domain interactions with numerous HBGA types. We showed that the GII.4 P domain HBGA interactions involved complex binding mechanisms that were not previously observed in norovirus structural studies. Many of the GII.4 P domain HBGA interactions we identified were negative in earlier ELISA-based studies. Altogether, we showed that the GII.4 norovirus P domains could accommodate numerous HBGA types.

 

== References ==

[[Category: Hansman, G S]]

[[Category: Singh, B K]]

[[Category: Viral capsid protein]]

[[Category: Viral protein]]