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| | <SX load='6ueb' size='340' side='right' viewer='molstar' caption='[[6ueb]], [[Resolution|resolution]] 3.30Å' scene=''> | | <SX load='6ueb' size='340' side='right' viewer='molstar' caption='[[6ueb]], [[Resolution|resolution]] 3.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ueb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Rabv Rabv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UEB OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6UEB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ueb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rabies_virus_SAD_B19 Rabies virus SAD B19]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UEB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UEB FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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">Electron Microscopy, [[Resolution|Resolution]] 3.3Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[http://proteopedia.org/fgij/fg.htm?mol=6ueb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ueb OCA], [http://pdbe.org/6ueb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ueb RCSB], [http://www.ebi.ac.uk/pdbsum/6ueb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ueb 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=6ueb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ueb OCA], [https://pdbe.org/6ueb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ueb RCSB], [https://www.ebi.ac.uk/pdbsum/6ueb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ueb ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/L_RABVS L_RABVS]] RNA-directed RNA polymerase that catalyzes the transcription of viral mRNAs, their capping and polyadenylation. The template is composed of the viral RNA tightly encapsidated by the nucleoprotein (N). The viral polymerase binds to the genomic RNA at the 3' leader promoter, and transcribes subsequently all viral mRNAs with a decreasing efficiency. The first gene is the most transcribed, and the last the least transcribed. The viral phosphoprotein acts as a processivity factor. Capping is concommitant with initiation of mRNA transcription. Indeed, a GDP polyribonucleotidyl transferase (PRNTase) adds the cap structure when the nascent RNA chain length has reached few nucleotides. Ribose 2'-O methylation of viral mRNA cap precedes and facilitates subsequent guanine-N-7 methylation, both acticities being carried by the viral polymerase. Polyadenylation of mRNAs occur by a stuttering mechanism at a slipery stop site present at the end viral genes. After finishing transcription of a mRNA, the polymerase can resume transcription of the downstream gene.[UniProtKB:P03523] RNA-directed RNA polymerase that catalyzes the replication of viral genomic RNA. The template is composed of the viral RNA tightly encapsidated by the nucleoprotein (N). The replicase mode is dependent on intracellular N protein concentration. In this mode, the polymerase replicates the whole viral genome without recognizing transcriptional signals, and the replicated genome is not caped or polyadenylated.[UniProtKB:P03523] | + | [https://www.uniprot.org/uniprot/PHOSP_RABVS PHOSP_RABVS] Non catalytic polymerase cofactor and regulatory protein that plays a role in viral transcription and replication. Stabilizes the RNA polymerase L to the N-RNA template and binds the soluble protein N, preventing it from encapsidating non-genomic RNA. Also inhibits host IFN-alpha and IFN-beta signaling by binding and retaining phosphorylated STAT1 in the cytoplasm or by inhibiting the DNA binding of STAT1 in the nucleus. Might be involved, through interaction with host dynein, in intracellular microtubule-dependent virus transport of incoming virus from the synapse toward the cell body (By similarity). Inhibits interferon induction pathways by interacting with host TBK1 and preventing the formation of dynamic cytoplasmic condensates that have liquid properties and that are essential for interferon production (PubMed:36640307).<ref>PMID:15557246</ref> <ref>PMID:36640307</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Nonsegmented negative-stranded (NNS) RNA viruses, among them the virus that causes rabies (RABV), include many deadly human pathogens. The large polymerase (L) proteins of NNS RNA viruses carry all of the enzymatic functions required for viral messenger RNA (mRNA) transcription and replication: RNA polymerization, mRNA capping, and cap methylation. We describe here a complete structure of RABV L bound with its phosphoprotein cofactor (P), determined by electron cryo-microscopy at 3.3 A resolution. The complex closely resembles the vesicular stomatitis virus (VSV) L-P, the one other known full-length NNS-RNA L-protein structure, with key local differences (e.g., in L-P interactions). Like the VSV L-P structure, the RABV complex analyzed here represents a preinitiation conformation. Comparison with the likely elongation state, seen in two structures of pneumovirus L-P complexes, suggests differences between priming/initiation and elongation complexes. Analysis of internal cavities within RABV L suggests distinct template and product entry and exit pathways during transcription and replication.
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| - | Structure of a rabies virus polymerase complex from electron cryo-microscopy.,Horwitz JA, Jenni S, Harrison SC, Whelan SPJ Proc Natl Acad Sci U S A. 2020 Jan 28;117(4):2099-2107. doi:, 10.1073/pnas.1918809117. Epub 2020 Jan 17. PMID:31953264<ref>PMID:31953264</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 6ueb" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </SX> | | </SX> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Rabv]] | + | [[Category: Rabies virus SAD B19]] |
| - | [[Category: Harrison, S C]] | + | [[Category: Harrison SC]] |
| - | [[Category: Horwitz, J A]] | + | [[Category: Horwitz JA]] |
| - | [[Category: Complex]]
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| - | [[Category: Phosphoprotein]]
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| - | [[Category: Polymerase]]
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| - | [[Category: Viral protein]]
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