7yet: Difference between revisions

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-'''Unreleased structure'''
-The entry 7yet is ON HOLD
+==The structure of EBOV L-VP35 in complex with suramin==
+<StructureSection load='7yet' size='340' side='right'caption='[[7yet]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7yet]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Ebola_virus Ebola virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7YET OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YET FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SVR:8,8-[CARBONYLBIS[IMINO-3,1-PHENYLENECARBONYLIMINO(4-METHYL-3,1-PHENYLENE)CARBONYLIMINO]]BIS-1,3,5-NAPHTHALENETRISULFONIC+ACID'>SVR</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=7yet FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yet OCA], [https://pdbe.org/7yet PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yet RCSB], [https://www.ebi.ac.uk/pdbsum/7yet PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yet ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/A0A1C4HDB0_9MONO A0A1C4HDB0_9MONO] 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.[ARBA:ARBA00003132][PIRNR:PIRNR037548]  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 activities 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.[PIRNR:PIRNR037548]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Filoviruses, including Ebola virus, pose an increasing threat to the public health. Although two therapeutic monoclonal antibodies have been approved to treat the Ebola virus disease(1,2), there are no approved broadly reactive drugs to control diverse filovirus infection. Filovirus has a large polymerase (L) protein and the cofactor viral protein 35 (VP35), which constitute the basic functional unit responsible for virus genome RNA synthesis(3). Owing to its conservation, the L-VP35 polymerase complex is a promising target for broadly reactive antiviral drugs. Here we determined the structure of Ebola virus L protein in complex with tetrameric VP35 using cryo-electron microscopy (state 1). Structural analysis revealed that Ebola virus L possesses a filovirus-specific insertion element that is essential for RNA synthesis, and that VP35 interacts extensively with the N-terminal region of L by three protomers of the VP35 tetramer. Notably, we captured the complex structure in a second conformation with the unambiguous priming loop and supporting helix away from polymerase active site (state 2). Moreover, we demonstrated that the century-old drug suramin could inhibit the activity of the Ebola virus polymerase in an enzymatic assay. The structure of the L-VP35-suramin complex reveals that suramin can bind at the highly conserved NTP entry channel to prevent substrates from entering the active site. These findings reveal the mechanism of Ebola virus replication and may guide the development of more powerful anti-filovirus drugs.
-Authors: Yi, S., Bin, Y., Qi, P.
+Structure of the Ebola virus polymerase complex.,Yuan B, Peng Q, Cheng J, Wang M, Zhong J, Qi J, Gao GF, Shi Y Nature. 2022 Oct;610(7931):394-401. doi: 10.1038/s41586-022-05271-2. Epub 2022 , Sep 28. PMID:36171293<ref>PMID:36171293</ref>
-Description: The structure of EBOV L-VP35 in complex with suramin
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Yi, S]]
+<div class="pdbe-citations 7yet" style="background-color:#fffaf0;"></div>
-[[Category: Bin, Y]]
-[[Category: Qi, P]]
+==See Also==
+*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Ebola virus]]
+[[Category: Large Structures]]
+[[Category: Peng Q]]
+[[Category: Shi Y]]
+[[Category: Yuan B]]