View source for 3sfg


==crystal structure of murine norovirus RNA dependent RNA polymerase in complex with 2thiouridine(2TU)==
<StructureSection load='3sfg' size='340' side='right'caption='[[3sfg]], [[Resolution|resolution]] 2.21&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3sfg]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Murine_norovirus_1 Murine norovirus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SFG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SFG 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]] 2.209&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2TU:1-(BETA-D-RIBOFURANOSYL)-2-THIOXO-2,3-DIHYDROPYRIMIDIN-4(1H)-ONE'>2TU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3sfg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sfg OCA], [https://pdbe.org/3sfg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sfg RCSB], [https://www.ebi.ac.uk/pdbsum/3sfg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sfg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/POLG_MNV1 POLG_MNV1] Induces the proliferation of the host smooth ER membranes forming long tubular structures (By similarity). These remodeled membranes probably form the viral factories that contain the replication complex (By similarity). May play a role in viral replication by interacting with host VAPA, a vesicle-associated membrane protein that plays a role in SNARE-mediated vesicle fusion. This interaction may target replication complex to intracellular membranes (Probable).[UniProtKB:P54634]<ref>PMID:28698274</ref>   Promotes intestinal tropism and persistent fecal shedding in strain CR6 (PubMed:23077309, PubMed:31130511, PubMed:31329638). This function requires Glu-94 and is present in persistant strains (PubMed:23077309).<ref>PMID:23077309</ref> <ref>PMID:31130511</ref> <ref>PMID:31329638</ref>   Displays NTPase activity, but probably no helicase activity (PubMed:30265237). Displays RNA chaperone-like activity and destabilizes dsRNA (PubMed:30265237). Induces the formation of convoluted membranes derived from the host ER (By similarity). These remodeled membranes probably form the viral factories that contain the replication complex (By similarity). Initiates host cell death by targeting the mitochondrial outer membrane, leading to the permeabilization of mitochondria, programmed host cell death and viral egress (PubMed:36991121). Externalization of host cardiolipin seems to be involved in the process (PubMed:36991121). Probably plays a role in preventing the assembly of host stress granules (PubMed:31905230).[UniProtKB:P54634]<ref>PMID:30265237</ref> <ref>PMID:31905230</ref> <ref>PMID:36991121</ref>   Probable key protein responsible for the formation of membrane alterations by the virus (By similarity). Induces the formation of convoluted membranes derived from the host ER (By similarity). These remodeled membranes probably form the viral factories that contain the replication complex (By similarity). May play a role in targeting replication complex to intracellular membranes.[UniProtKB:P54634]  Viral genome-linked protein is covalently linked to the 5'-end of the positive-strand, negative-strand genomic RNAs and subgenomic RNA (By similarity). Acts as a genome-linked replication primer (By similarity). May recruit ribosome to viral RNA thereby promoting viral proteins translation (By similarity). Interacts with host translation initiation complex to allow the translation of viral proteins (PubMed:16835235, PubMed:24928504). Induces the formation of aggregates of RNA-directed RNA polymerase in the presence of RNA (PubMed:30038601). Through its interaction with the viral RNA-directed RNA polymerase, plays a crucial role in enhancing the polymerase activity (PubMed:30038601).[UniProtKB:P27409]<ref>PMID:16835235</ref> <ref>PMID:24928504</ref> <ref>PMID:30038601</ref>   Processes the polyprotein. 3CLpro-RdRp is first released by autocleavage, then all other proteins are cleaved (PubMed:26363064). May cleave host polyadenylate-binding protein thereby inhibiting cellular translation. Does not cleave host G3BP1 (PubMed:27147742).<ref>PMID:26363064</ref> <ref>PMID:27147742</ref>   Replicates genomic and antigenomic RNA by recognizing replications specific signals. Transcribes also a subgenomic mRNA by initiating RNA synthesis internally on antigenomic RNA. This sgRNA codes for structural proteins. Catalyzes the covalent attachment VPg with viral RNAs (By similarity).[UniProtKB:Q86119]
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== Publication Abstract from PubMed ==
Murine norovirus-1 (MNV-1) shares many features with human norovirus (HuNoV) and both are classified within the norovirus genus of Caliciviridae family. MNV-1 is used as the surrogate for HuNoV research since it is the only form that can be grown in cell culture. HuNoV and MNV-1 RNA dependent RNA polymerase (RdRp) proteins with the sequence identity of 59% show essentially identical conformations. Here we report the first structural evidence of 2-thiouridine (2TU) or ribavirin binding to MNV-1 RdRp, based on the crystal structures determined at 2.2A and 2.5A resolutions, respectively. Cellular and biochemical studies revealed stronger inhibitory effect of 2TU on the replication of MNV-1 in RAW 264.7 cells, compared to that of ribavirin. Our complex structures highlight the key interactions involved in recognition of the nucleoside analogs which block the active site of the viral RNA polymerase.

Crystal structures of murine norovirus-1 RNA-dependent RNA polymerase in complex with 2-thiouridine or ribavirin.,Alam I, Lee JH, Cho KJ, Han KR, Yang JM, Chung MS, Kim KH Virology. 2012 May 10;426(2):143-51. Epub 2012 Feb 16. PMID:22341781<ref>PMID:22341781</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3sfg" style="background-color:#fffaf0;"></div>

==See Also==
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Murine norovirus 1]]
[[Category: Alam I]]
[[Category: Kim KH]]