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3rkd

From Proteopedia

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Hepatitis E Virus E2s domain (Genotype I) in complex with a neutralizing antibody

Structural highlights

3rkd is a 6 chain structure with sequence from Mus musculus and Orthohepevirus A. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.9Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CAPSD_HEVPA Major viral capsid protein that encapsidates the viral genome. Binds to the 5' end of the genomic RNA (By similarity).

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.

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3rkd"

Categories: Large Structures | Mus musculus | Orthohepevirus A | Sivaraman J | Tang XH

@@ Line 3: / Line 3: @@
 <StructureSection load='3rkd' size='340' side='right'caption='[[3rkd]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<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>
+<table><tr><td colspan='2'>[[3rkd]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Orthohepevirus_A Orthohepevirus A]. 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"><div style='overflow: auto; max-height: 3em;'>[[3rkc|3rkc]]</div></td></tr>
+</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='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'>[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>
+== Function ==
+[https://www.uniprot.org/uniprot/CAPSD_HEVPA CAPSD_HEVPA] Major viral capsid protein that encapsidates the viral genome. Binds to the 5' end of the genomic RNA (By similarity).
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Hev]]
 [[Category: Large Structures]]
 [[Category: Mus musculus]]
-[[Category: Sivaraman, J]]
+[[Category: Orthohepevirus A]]
-[[Category: Tang, X H]]
+[[Category: Sivaraman J]]
-[[Category: Hepatitis e virus capsid protein]]
+[[Category: Tang XH]]
-[[Category: Neutralizing antibody]]
-[[Category: Viral protein-immune system complex]]

3rkd

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Current revision

Hepatitis E Virus E2s domain (Genotype I) in complex with a neutralizing antibody

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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