8as6

Structure of the SFTSV L protein bound to 5' cRNA hook [5' HOOK]

spinqualitylabelsall models 8as6, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8as6 is a 2 chain structure with sequence from SFTS virus AH12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.4Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function U3GU88_SFTS 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also RNA polymerase 3D structures

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