5D98

Influenza C Virus RNA-dependent RNA Polymerase - Space group P43212

5D98 の概要

• エントリーDOI: 10.2210/pdb5d98/pdb
• 関連するPDBエントリー: 5D9A
• 分子名称: Polymerase acidic protein, RNA-directed RNA polymerase catalytic subunit, Polymerase basic protein 2, ... (4 entities in total)
• 機能のキーワード: rna-dependent rna polymerase, influenza, influenza c virus, negative-strand virus, transferase-rna complex, transferase/rna
• 由来する生物種: Influenza C virus (strain C/Johannesburg/1/1966); 詳細
• 細胞内の位置: Host cytoplasm : Q9IMP5; Host nucleus : Q9IMP4; Virion : Q9IMP3
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 514385.27

構造登録者

Hengrung, N.,El Omari, K.,Serna Martin, I.,Vreede, F.T.,Cusack, S.,Rambo, R.P.,Vonrhein, C.,Bricogne, G.,Stuart, D.I.,Grimes, J.M.,Fodor, E. (登録日: 2015-08-18, 公開日: 2015-10-21, 最終更新日: 2024-11-20)

主引用文献

Hengrung, N.,El Omari, K.,Serna Martin, I.,Vreede, F.T.,Cusack, S.,Rambo, R.P.,Vonrhein, C.,Bricogne, G.,Stuart, D.I.,Grimes, J.M.,Fodor, E.
Crystal structure of the RNA-dependent RNA polymerase from influenza C virus.
Nature, 527:114-117, 2015

PubMed Abstract: Negative-sense RNA viruses, such as influenza, encode large, multidomain RNA-dependent RNA polymerases that can both transcribe and replicate the viral RNA genome. In influenza virus, the polymerase (FluPol) is composed of three polypeptides: PB1, PB2 and PA/P3. PB1 houses the polymerase active site, whereas PB2 and PA/P3 contain, respectively, cap-binding and endonuclease domains required for transcription initiation by cap-snatching. Replication occurs through de novo initiation and involves a complementary RNA intermediate. Currently available structures of the influenza A and B virus polymerases include promoter RNA (the 5' and 3' termini of viral genome segments), showing FluPol in transcription pre-initiation states. Here we report the structure of apo-FluPol from an influenza C virus, solved by X-ray crystallography to 3.9 Å, revealing a new 'closed' conformation. The apo-FluPol forms a compact particle with PB1 at its centre, capped on one face by PB2 and clamped between the two globular domains of P3. Notably, this structure is radically different from those of promoter-bound FluPols. The endonuclease domain of P3 and the domains within the carboxy-terminal two-thirds of PB2 are completely rearranged. The cap-binding site is occluded by PB2, resulting in a conformation that is incompatible with transcription initiation. Thus, our structure captures FluPol in a closed, transcription pre-activation state. This reveals the conformation of newly made apo-FluPol in an infected cell, but may also apply to FluPol in the context of a non-transcribing ribonucleoprotein complex. Comparison of the apo-FluPol structure with those of promoter-bound FluPols allows us to propose a mechanism for FluPol activation. Our study demonstrates the remarkable flexibility of influenza virus RNA polymerase, and aids our understanding of the mechanisms controlling transcription and genome replication.

PubMed: 26503046
DOI: 10.1038/nature15525

実験手法

X-RAY DIFFRACTION (3.9 Å)