8as6: Difference between revisions
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==Structure of the SFTSV L protein bound to 5' cRNA hook [5' HOOK]== | |||
<StructureSection load='8as6' size='340' side='right'caption='[[8as6]], [[Resolution|resolution]] 3.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8as6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/SFTS_virus_AH12 SFTS virus AH12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8AS6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8AS6 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]] 3.4Å</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=8as6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8as6 OCA], [https://pdbe.org/8as6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8as6 RCSB], [https://www.ebi.ac.uk/pdbsum/8as6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8as6 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/U3GU88_SFTS U3GU88_SFTS] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a phenuivirus that has rapidly become endemic in several East Asian countries. The large (L) protein of SFTSV, which includes the RNA-dependent RNA polymerase (RdRp), is responsible for catalysing viral genome replication and transcription. Here, we present 5 cryo-electron microscopy (cryo-EM) structures of the L protein in several states of the genome replication process, from pre-initiation to late-stage elongation, at a resolution of up to 2.6 A. We identify how the L protein binds the 5' viral RNA in a hook-like conformation and show how the distal 5' and 3' RNA ends form a duplex positioning the 3' RNA terminus in the RdRp active site ready for initiation. We also observe the L protein stalled in the early and late stages of elongation with the RdRp core accommodating a 10-bp product-template duplex. This duplex ultimately splits with the template binding to a designated 3' secondary binding site. The structural data and observations are complemented by in vitro biochemical and cell-based mini-replicon assays. Altogether, our data provide novel key insights into the mechanism of viral genome replication by the SFTSV L protein and will aid drug development against segmented negative-strand RNA viruses. | |||
Structural insights into viral genome replication by the severe fever with thrombocytopenia syndrome virus L protein.,Williams HM, Thorkelsson SR, Vogel D, Milewski M, Busch C, Cusack S, Grunewald K, Quemin ERJ, Rosenthal M Nucleic Acids Res. 2023 Feb 22;51(3):1424-1442. doi: 10.1093/nar/gkac1249. PMID:36651274<ref>PMID:36651274</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8as6" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[RNA polymerase 3D structures|RNA polymerase 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Williams | [[Category: Large Structures]] | ||
[[Category: SFTS virus AH12]] | |||
[[Category: Busch C]] | |||
[[Category: Cusack S]] | |||
[[Category: Grunewald K]] | |||
[[Category: Milewski M]] | |||
[[Category: Quemin ERJ]] | |||
[[Category: Rosenthal M]] | |||
[[Category: Thorkelsson SR]] | |||
[[Category: Vogel D]] | |||
[[Category: Williams HM]] | |||
Latest revision as of 09:45, 24 July 2024
Structure of the SFTSV L protein bound to 5' cRNA hook [5' HOOK]Structure of the SFTSV L protein bound to 5' cRNA hook [5' HOOK]
Structural highlights
FunctionPublication Abstract from PubMedSevere fever with thrombocytopenia syndrome virus (SFTSV) is a phenuivirus that has rapidly become endemic in several East Asian countries. The large (L) protein of SFTSV, which includes the RNA-dependent RNA polymerase (RdRp), is responsible for catalysing viral genome replication and transcription. Here, we present 5 cryo-electron microscopy (cryo-EM) structures of the L protein in several states of the genome replication process, from pre-initiation to late-stage elongation, at a resolution of up to 2.6 A. We identify how the L protein binds the 5' viral RNA in a hook-like conformation and show how the distal 5' and 3' RNA ends form a duplex positioning the 3' RNA terminus in the RdRp active site ready for initiation. We also observe the L protein stalled in the early and late stages of elongation with the RdRp core accommodating a 10-bp product-template duplex. This duplex ultimately splits with the template binding to a designated 3' secondary binding site. The structural data and observations are complemented by in vitro biochemical and cell-based mini-replicon assays. Altogether, our data provide novel key insights into the mechanism of viral genome replication by the SFTSV L protein and will aid drug development against segmented negative-strand RNA viruses. Structural insights into viral genome replication by the severe fever with thrombocytopenia syndrome virus L protein.,Williams HM, Thorkelsson SR, Vogel D, Milewski M, Busch C, Cusack S, Grunewald K, Quemin ERJ, Rosenthal M Nucleic Acids Res. 2023 Feb 22;51(3):1424-1442. doi: 10.1093/nar/gkac1249. PMID:36651274[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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