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-Structure paper
タイトル | Structural snapshots of phenuivirus cap-snatching and transcription. |
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ジャーナル・号・ページ | Nucleic Acids Res, Vol. 52, Issue 10, Page 6049-6065, Year 2024 |
掲載日 | 2024年6月10日 |
著者 | Harry M Williams / Sigurdur R Thorkelsson / Dominik Vogel / Carola Busch / Morlin Milewski / Stephen Cusack / Kay Grünewald / Emmanuelle R J Quemin / Maria Rosenthal / |
PubMed 要旨 | Severe fever with thrombocytopenia syndrome virus (SFTSV) is a human pathogen that is now endemic to several East Asian countries. The viral large (L) protein catalyzes viral transcription by ...Severe fever with thrombocytopenia syndrome virus (SFTSV) is a human pathogen that is now endemic to several East Asian countries. The viral large (L) protein catalyzes viral transcription by stealing host mRNA caps via a process known as cap-snatching. Here, we establish an in vitro cap-snatching assay and present three high-quality electron cryo-microscopy (cryo-EM) structures of the SFTSV L protein in biologically relevant, transcription-specific states. In a priming-state structure, we show capped RNA bound to the L protein cap-binding domain (CBD). The L protein conformation in this priming structure is significantly different from published replication-state structures, in particular the N- and C-terminal domains. The capped-RNA is positioned in a way that it can feed directly into the RNA-dependent RNA polymerase (RdRp) ready for elongation. We also captured the L protein in an early-elongation state following primer-incorporation demonstrating that this priming conformation is retained at least in the very early stages of primer extension. This structural data is complemented by in vitro biochemical and cell-based assays. Together, these insights further our mechanistic understanding of how SFTSV and other bunyaviruses incorporate stolen host mRNA fragments into their viral transcripts thereby allowing the virus to hijack host cell translation machinery. |
リンク | Nucleic Acids Res / PubMed:38709882 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.98 - 3.4 Å |
構造データ | EMDB-18963, PDB-8r6u: EMDB-18967, PDB-8r6w: EMDB-18969, PDB-8r6y: |
化合物 | ChemComp-MG: ChemComp-2KH: |
由来 |
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キーワード | VIRAL PROTEIN / SFTSV / RNA-DEPENDENT RNA POLYMERASE / VIRAL RNA |