6nu9: Difference between revisions

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<StructureSection load='6nu9' size='340' side='right'caption='[[6nu9]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
<StructureSection load='6nu9' size='340' side='right'caption='[[6nu9]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6nu9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Hev Hev]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NU9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NU9 FirstGlance]. <br>
<table><tr><td colspan='2'>[[6nu9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Orthohepevirus_A Orthohepevirus A]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NU9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NU9 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NO2:NITRITE+ION'>NO2</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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]] 1.761&#8491;</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=6nu9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nu9 OCA], [http://pdbe.org/6nu9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nu9 RCSB], [http://www.ebi.ac.uk/pdbsum/6nu9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nu9 ProSAT]</span></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=NO2:NITRITE+ION'>NO2</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6nu9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nu9 OCA], [https://pdbe.org/6nu9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nu9 RCSB], [https://www.ebi.ac.uk/pdbsum/6nu9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nu9 ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/POLN_HEVPA POLN_HEVPA] Methyltransferase: Displays a capping enzyme activity. This function is necessary since all viral RNAs are synthesized in the cytoplasm, and host capping enzymes are restricted to the nucleus. The enzymatic reaction involves a covalent link between 7-methyl-GMP and the methyltransferase, whereas eukaryotic capping enzymes form a covalent complex only with GMP. Methyltransferase catalyzes transfer of a methyl group from S-adenosylmethionine to GTP and GDP to yield m(7)GTP or m(7)GDP. GDP is a better substrate than GTP. This enzyme also displays guanylyltransferase activity to form a covalent complex, methyltransferase-m(7)GMP, from which 7-methyl-GMP is transferred to the mRNA to create the cap structure.[UniProtKB:Q81862]  Y-domain: Indispensable for virus replication.[UniProtKB:Q81862]  Putative protease: May participate in the processing of polyprotein pORF1 and capsid protein ORF2, possibly together with cellular proteases. Inhibits induction of IFN-beta by MDA5 and RIG-I pathways and down-regulates the expression of MDA5.[UniProtKB:Q81862]  NTPase/helicase: Multi-functional protein that exhibits NTPase and RNA unwinding activities (By similarity). Hydrolyzes all NTPs efficiently and unwinds RNA duplexes containing 5' overhangs (By similarity). Possesses a sequence independent RNA-5'-triphosphatase (RTPase) activity suggestive of its role in forming viral cap structure. Participates also in viral genome replication, RNA translocation and genome packaging/unpackaging (By similarity).[UniProtKB:P29324][UniProtKB:Q81862]  RNA-directed RNA polymerase: Plays an essential role in the virus replication (By similarity). Binds to the 3'-end of the genomic RNA to initiate viral replication (By similarity).[UniProtKB:Q81862][UniProtKB:Q9WC28]
Hepatitis E virus (HEV) is a 7.2 kb positive-sense, single-stranded RNA virus containing three partially overlapping reading frames, ORF 1-3. All non-structural proteins required for viral replication are encoded by ORF1 and are transcribed as a single transcript. Computational analysis of the complete ORF1 polyprotein identified a previously uncharacterized region of predicted secondary structure bordered by two disordered regions coinciding partially with a region predicted as a putative cysteine protease. Following successful cloning, expression and purification of this region, the crystal structure of the identified protein was determined and identified to have considerable structural homology to a fatty acid binding domain. Further analysis of the structure revealed a metal binding site, shown unambiguously to specifically bind zinc via a non-classical, potentially catalytic zinc-binding motif. Based on the structural homology of the HEV protein with known structures, along with the presence of a catalytic zinc-binding motif, it is possible that the identified protein corresponds to the HEV protease, which could require activation or repression through the binding of a fatty acid. This represents a significant step forward in the characterization and the understanding of the molecular mechanisms of the HEV genome. We present analysis for the first time of this identified non-structural protein, expanding the knowledge and understanding of the complex mechanisms of HEV biology.IMPORTANCE Hepatitis E virus (HEV) is an emerging virus found predominately in developing countries causing an estimated 20 million infections, which result in approximately 57,000 deaths a year. Although it is known that the non-structural proteins of the HEV ORF1 are expressed as a single transcript, there is debate as to whether ORF1 functions as a single polyprotein or if it is processed into separate domains via a viral or endogenous cellular protease. In the following paper, we present the first structural and biophysical characterization of a HEV non-structural protein using a construct that has partially overlapping boundaries with the predicted putative cysteine protease.
 
First Crystal Structure of a Non-Structural Hepatitis E Viral Protein Identifies a Putative Novel Zinc-Binding Protein.,Proudfoot A, Hyrina A, Holdorf M, Frank AO, Bussiere D J Virol. 2019 Apr 24. pii: JVI.00170-19. doi: 10.1128/JVI.00170-19. PMID:31019049<ref>PMID:31019049</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6nu9" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Hev]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Bussiere, D]]
[[Category: Orthohepevirus A]]
[[Category: Proudfoot, A]]
[[Category: Bussiere D]]
[[Category: Non-structural protein]]
[[Category: Proudfoot A]]
[[Category: Viral protein]]
[[Category: Zinc-binding]]

Latest revision as of 14:49, 13 March 2024

Crystal Structure of a Zinc-Binding Non-Structural Protein from the Hepatitis E Virus

6nu9, resolution 1.76Å

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