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Structure paper

タイトル	Structural snapshots of actively transcribing influenza polymerase.
ジャーナル・号・ページ	Nat Struct Mol Biol, Vol. 26, Issue 6, Page 460-470, Year 2019
掲載日	2019年6月3日
著者	Tomas Kouba / Petra Drncová / Stephen Cusack /
PubMed 要旨	Influenza virus RNA-dependent RNA polymerase uses unique mechanisms to transcribe its single-stranded genomic viral RNA (vRNA) into messenger RNA. The polymerase is initially bound to a promoter ...Influenza virus RNA-dependent RNA polymerase uses unique mechanisms to transcribe its single-stranded genomic viral RNA (vRNA) into messenger RNA. The polymerase is initially bound to a promoter comprising the partially base-paired 3' and 5' extremities of the RNA. A short, capped primer, 'cap-snatched' from a nascent host polymerase II transcript, is directed towards the polymerase active site to initiate RNA synthesis. Here we present structural snapshots, as determined by X-ray crystallography and cryo-electron microscopy, of actively initiating influenza polymerase as it transitions towards processive elongation. Unexpected conformational changes unblock the active site cavity to allow establishment of a nine-base-pair template-product RNA duplex before the strands separate into distinct exit channels. Concomitantly, as the template translocates, the promoter base pairs are broken and the template entry region is remodeled. These structures reveal details of the influenza polymerase active site that will help optimize nucleoside analogs or other compounds that directly inhibit viral RNA synthesis.
リンク	Nat Struct Mol Biol / PubMed:31160782 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	2.88 - 3.24 Å
構造データ	4511 6qcs EMDB-4511, PDB-6qcs: Influenza B polymerase pre-initiation complex 手法: EM (単粒子) / 解像度: 3.1 Å 4512 6qct EMDB-4512, PDB-6qct: Influenza B polymerase elongation complex 手法: EM (単粒子) / 解像度: 3.2 Å PDB-6qcv: Crystal structure of influenza B polymerase initiation state with capped 14-mer RNA primer and CTP 手法: X-RAY DIFFRACTION / 解像度: 3.24 Å PDB-6qcw: Crystal structure of influenza B polymerase initiation state with capped 14-mer RNA primer 手法: X-RAY DIFFRACTION / 解像度: 2.88 Å PDB-6qcx: Crystal structure of influenza B polymerase initiation state with capped 15-mer RNA primer 手法: X-RAY DIFFRACTION / 解像度: 3.08 Å
化合物	ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-PO4: PHOSPHATE ION / ホスファ-ト ChemComp-CTP: CYTIDINE-5'-TRIPHOSPHATE / CTP ChemComp-POP: PYROPHOSPHATE 2-
由来	influenza b virus (B型インフルエンザウイルス) influenza b virus (b/memphis/13/2003) (B型インフルエンザウイルス) synthetic construct (人工物)
キーワード	VIRAL PROTEIN / Influenza polzmerase / Influenza B Polymerase / RNA dependent RNA polymerase