View source for 4p26


==Structure of the P domain from a GI.7 Norovirus variant in complex with A-type 2 HBGA==
<StructureSection load='4p26' size='340' side='right'caption='[[4p26]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4p26]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Norovirus_Hu/GI.7/TCH-060/USA/2003 Norovirus Hu/GI.7/TCH-060/USA/2003]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P26 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P26 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A2G:N-ACETYL-2-DEOXY-2-AMINO-GALACTOSE'>A2G</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PRD_900132:Blood+group+A+H+type+2+antigen,+beta+anomer'>PRD_900132</scene></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=4p26 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p26 OCA], [https://pdbe.org/4p26 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p26 RCSB], [https://www.ebi.ac.uk/pdbsum/4p26 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p26 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/G8FL04_9CALI G8FL04_9CALI] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human noroviruses (NoVs) cause acute epidemic gastroenteritis. Susceptibility to the majority of NoV infections is determined by genetically controlled secretor-dependent expression of histo-blood group antigens (HBGAs), which are also critical for NoV attachment to host cells. Human NoVs are classified into two major genogroups (GI and GII) with each genogroup further divided into several genotypes. GII NoVs are more prevalent and exhibit periodic emergence of new variants, suggested to be driven by altered HBGA-binding specificities and antigenic drift. Recent epidemiologic studies show increased activity among GI NoVs with some members showing the ability to bind non-secretor HBGAs. NoVs bind HBGAs through the protruding (P) domain of the major capsid protein VP1. GI NoVs, similar to GII, exhibit significant sequence variations in the P domain; it is unclear how these variations affect HBGA binding specificities. To understand the determinants of possible strain-specific HBGA binding among GI NoVs, we determined the structure of the P domain of a GI.7 clinical isolate and compared it to the P domain structures of previously determined GI.1 and GI.2 strains. Our crystallographic studies revealed significant structural differences particularly in the loop regions of the GI.7 P domain altering its surface topography and electrostatic landscape and potentially indicating antigenic variation. The GI.7 strain bound to H- and A-type, Lewis secretor and Lewis non-secretor families of HBGAs allowing us to further elucidate the structural determinants of non-secretor HBGA binding among GI NoVs and to infer several contrasting and generalizable features of HBGA binding in the GI NoVs. IMPORTANCE: Human noroviruses (NoVs) cause acute epidemic gastroenteritis. Recent epidemiological studies have shown increased prevalence of genogroup I (GI) NoVs. Although secretor-positive status is strongly correlated with NoV infection, cases of NoV infection associated with secretor-negative individuals are reported. Biochemical studies have shown that GI NoVs exhibit genotype-dependent binding to non-secretor histo blood group antigens (HBGAs). From our crystallographic studies of a GI.7 NoV, in comparison with previous studies on GI.1 and G1.2 NoVs, we show genotypic differences translate to extensive structural changes in the loop regions that significantly alter the surface topography and electrostatic landscape of the P domain; these features may be indicative of antigenic variations contributing to serotypic differentiation in GI NoVs, and also differential modulation of the HBGA binding characteristics. A significant finding is that the threshold length and the structure of one of the loops are critical determinants in the GI NoVs binding to non-secretor HBGAs.

Structural Analysis of Determinants to HBGA Binding Specificity in GI Noroviruses.,Shanker S, Czako R, Sankaran B, Atmar RL, Estes MK, Prasad BV J Virol. 2014 Mar 19. PMID:24648450<ref>PMID:24648450</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4p26" style="background-color:#fffaf0;"></div>

==See Also==
*[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Norovirus Hu/GI 7/TCH-060/USA/2003]]
[[Category: Atmar R]]
[[Category: Czako R]]
[[Category: Estes M]]
[[Category: Prasad BVV]]
[[Category: Sankaran B]]
[[Category: Shanker S]]