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| | ==Hepatitis E Virus E2s domain (Genotype I) in complex with a neutralizing antibody== | | ==Hepatitis E Virus E2s domain (Genotype I) in complex with a neutralizing antibody== |
| - | <StructureSection load='3rkd' size='340' side='right' caption='[[3rkd]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='3rkd' size='340' side='right'caption='[[3rkd]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3rkd]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Hev Hev] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RKD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RKD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3rkd]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Hev Hev] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RKD FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3rkc|3rkc]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3rkc|3rkc]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ORF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=12461 HEV])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ORF2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=12461 HEV])</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=3rkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rkd OCA], [http://pdbe.org/3rkd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3rkd RCSB], [http://www.ebi.ac.uk/pdbsum/3rkd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3rkd ProSAT]</span></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=3rkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rkd OCA], [https://pdbe.org/3rkd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rkd RCSB], [https://www.ebi.ac.uk/pdbsum/3rkd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rkd ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | ==See Also== | | ==See Also== |
| - | *[[3D structures of monoclonal antibody|3D structures of monoclonal antibody]] | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | + | *[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Hev]] | | [[Category: Hev]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| | [[Category: Sivaraman, J]] | | [[Category: Sivaraman, J]] |
| Structural highlights
Publication Abstract from PubMed
Hepatitis E virus (HEV) causes acute hepatitis in humans, predominantly by contamination of food and water, and is characterized by jaundice and flu-like aches and pains. To date, no vaccines are commercially available to prevent the disease caused by HEV. Previously, we showed that a monoclonal antibody, 8C11, specifically recognizes a neutralizing conformational epitope on HEV genotype I. The antibody 8C11 blocks the virus-like particle from binding to and penetrating the host cell. Here, we report the complex crystal structure of 8C11 Fab with HEV E2s(I) domain at 1.9 A resolution. The 8C11 epitopes on E2s(I) were identified at Asp(496)-Thr(499), Val(510)-Leu(514), and Asn(573)-Arg(578). Mutations and cell-model assays identified Arg(512) as the most crucial residue for 8C11 interaction with and neutralization of HEV. Interestingly, 8C11 specifically neutralizes HEV genotype I, but not the other genotypes. Because HEV type I and IV are the most abundant genotypes, to understand this specificity further we determined the structure of E2s(IV) at 1.79 A resolution and an E2s(IV) complex with 8C11 model was generated. The comparison between the 8C11 complexes with type I and IV revealed the key residues that distinguish these two genotypes. Of particular interest, the residue at amino acid position 497 at the 8C11 epitope region of E2s is distinct among these two genotypes. Swapping this residue from one genotype to another inversed the 8C11 reactivity, demonstrating the essential role played by amino acid 497 in the genotype recognition. These studies may lead to the development of antibody-based drugs for the specific treatment against HEV.
Structural basis for the neutralization and genotype specificity of hepatitis E virus.,Tang X, Yang C, Gu Y, Song C, Zhang X, Wang Y, Zhang J, Hew CL, Li S, Xia N, Sivaraman J Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10266-71. Epub 2011 Jun 3. PMID:21642534[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tang X, Yang C, Gu Y, Song C, Zhang X, Wang Y, Zhang J, Hew CL, Li S, Xia N, Sivaraman J. Structural basis for the neutralization and genotype specificity of hepatitis E virus. Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10266-71. Epub 2011 Jun 3. PMID:21642534 doi:10.1073/pnas.1101309108
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