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New page: left|200px<br /><applet load="2dwr" size="350" color="white" frame="true" align="right" spinBox="true" caption="2dwr, resolution 2.50Å" /> '''Crystal structure of...
 
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[[Image:2dwr.jpg|left|200px]]<br /><applet load="2dwr" size="350" color="white" frame="true" align="right" spinBox="true"
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'''Crystal structure of the human Wa rotavirus VP8* carbohydrate-recognising domain'''<br />


==Overview==
==Crystal structure of the human Wa rotavirus VP8* carbohydrate-recognising domain==
Rotavirus infection leads to the death of half a million children, annually. The exact specifics of interaction between rotavirus particles, and host cells enabling invasion and infection have remained elusive. Host, cell oligosaccharides are critical components, and their involvement aids, the virus in cell-recognition and attachment, as well as dictation of the, remarkable host-specificity that rotaviruses demonstrate. Interaction, between the rotavirus spike-protein carbohydrate-binding domain (VP8*) and, cell surface oligosaccharides facilitate virus recognition of host cells, and attachment. Rotaviruses are considered, controversially, to recognise, vastly different carbohydrate structures and either with incorporation of, terminal sialic acid or without, as assessed by their ability to infect, cells that have been pre-treated with sialidases. Herein, the X-ray, crystallographic structures of VP8* from the sialidase insensitive Wa and, the sialidase sensitive CRW-8 rotavirus strains that cause debilitating, gastroenteritis in human and pig are reported. Striking differences are, apparent regarding recognition of the sialic acid derivative methyl, alpha-d-N-acetylneuraminide, presenting the first experimental evidence of, the inability of the human rotavirus strain to bind this monosaccharide, that correlates with Wa and CRW-8 recognising sialidase-resistant and, sialidase-sensitive receptors, respectively. Identified are structural, features that provide insight in attainment of substrate specificity, exhibited by porcine strains as compared to rhesus rotavirus. Revealed in, the CRW-8 VP8* structure is an additional bound ligand that intriguingly, is within a cleft located equivalent to the carbohydrate-binding region of, galectins, and is suggestive of a new region for interaction with, cell-surface carbohydrates. This novel result and detailed comparison of, our representative sialidase-sensitive CRW-8 and insensitive Wa VP8*, structures with those reported leads to our hypothesis that this groove is, used for binding carbohydrates, and that for the human strains, as for, other sialidase-insensitive strains could represent a major, oligosaccharide-binding region.
<StructureSection load='2dwr' size='340' side='right'caption='[[2dwr]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2dwr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_rotavirus_A Human rotavirus A]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DWR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DWR 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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</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=2dwr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dwr OCA], [https://pdbe.org/2dwr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2dwr RCSB], [https://www.ebi.ac.uk/pdbsum/2dwr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2dwr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/VP4_ROTHW VP4_ROTHW] Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus entry into the host cell probably involves multiple sequential contacts between the outer capsid proteins VP4 and VP7, and the cell receptors. According to the considered strain, VP4 seems to essentially target sialic acid and/or the integrin heterodimer ITGA2/ITGB1.  Outer capsid protein VP5*: forms the spike "foot" and "body". Acts as a membrane permeabilization protein that mediates release of viral particles from endosomal compartments into the cytoplasm. In integrin-dependent strains, VP5* targets the integrin heterodimer ITGA2/ITGB1 for cell attachment. VP8* forms the head of the spikes. It is the viral hemagglutinin and an important target of neutralizing antibodies. In sialic acid-dependent strains, VP8* binds to host cell sialic acid, most probably a ganglioside, providing the initial contact (By similarity).
== 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/dw/2dwr_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2dwr ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
2DWR is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_rotavirus_a Human rotavirus a] with <scene name='pdbligand=GOL:'>GOL</scene> and <scene name='pdbligand=IOH:'>IOH</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DWR OCA].
*[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
Insight into Host Cell Carbohydrate-recognition by Human and Porcine Rotavirus from Crystal Structures of the Virion Spike Associated Carbohydrate-binding Domain (VP8*)., Blanchard H, Yu X, Coulson BS, von Itzstein M, J Mol Biol. 2007 Apr 6;367(4):1215-26. Epub 2007 Jan 13. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17306299 17306299]
[[Category: Human rotavirus A]]
[[Category: Human rotavirus a]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Blanchard H]]
[[Category: Blanchard, H.]]
[[Category: GOL]]
[[Category: IOH]]
[[Category: beta-sandwich]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 19:13:48 2008''

Latest revision as of 09:25, 3 April 2024

Crystal structure of the human Wa rotavirus VP8* carbohydrate-recognising domainCrystal structure of the human Wa rotavirus VP8* carbohydrate-recognising domain

Structural highlights

2dwr is a 1 chain structure with sequence from Human rotavirus A. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.5Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

VP4_ROTHW Spike-forming protein that mediates virion attachment to the host epithelial cell receptors and plays a major role in cell penetration, determination of host range restriction and virulence. Rotavirus entry into the host cell probably involves multiple sequential contacts between the outer capsid proteins VP4 and VP7, and the cell receptors. According to the considered strain, VP4 seems to essentially target sialic acid and/or the integrin heterodimer ITGA2/ITGB1. Outer capsid protein VP5*: forms the spike "foot" and "body". Acts as a membrane permeabilization protein that mediates release of viral particles from endosomal compartments into the cytoplasm. In integrin-dependent strains, VP5* targets the integrin heterodimer ITGA2/ITGB1 for cell attachment. VP8* forms the head of the spikes. It is the viral hemagglutinin and an important target of neutralizing antibodies. In sialic acid-dependent strains, VP8* binds to host cell sialic acid, most probably a ganglioside, providing the initial contact (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

2dwr, resolution 2.50Å

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