7NKA

1918 H1N1 Viral influenza polymerase heterotrimer with Nb8206

7NKA の概要

• エントリーDOI: 10.2210/pdb7nka/pdb
• EMDBエントリー: 12435
• 分子名称: Polymerase acidic protein, RNA-directed RNA polymerase catalytic subunit, Polymerase basic protein 2,Polymerase basic protein 2, ... (6 entities in total)
• 機能のキーワード: influenza, rna polymerase, h1n1, 1918, viral protein, nanobody
• 由来する生物種: Influenza A virus (A/Brevig Mission/1/1918(H1N1)); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 296112.54

構造登録者

Keown, J.R.,Carrique, L.,Fodor, E.,Grimes, J.M. (登録日: 2021-02-17, 公開日: 2021-12-01, 最終更新日: 2024-10-23)

主引用文献

Keown, J.R.,Zhu, Z.,Carrique, L.,Fan, H.,Walker, A.P.,Serna Martin, I.,Pardon, E.,Steyaert, J.,Fodor, E.,Grimes, J.M.
Mapping inhibitory sites on the RNA polymerase of the 1918 pandemic influenza virus using nanobodies.
Nat Commun, 13:251-251, 2022

PubMed Abstract: Influenza A viruses cause seasonal epidemics and global pandemics, representing a considerable burden to healthcare systems. Central to the replication cycle of influenza viruses is the viral RNA-dependent RNA polymerase which transcribes and replicates the viral RNA genome. The polymerase undergoes conformational rearrangements and interacts with viral and host proteins to perform these functions. Here we determine the structure of the 1918 influenza virus polymerase in transcriptase and replicase conformations using cryo-electron microscopy (cryo-EM). We then structurally and functionally characterise the binding of single-domain nanobodies to the polymerase of the 1918 pandemic influenza virus. Combining these functional and structural data we identify five sites on the polymerase which are sensitive to inhibition by nanobodies. We propose that the binding of nanobodies at these sites either prevents the polymerase from assuming particular functional conformations or interactions with viral or host factors. The polymerase is highly conserved across the influenza A subtypes, suggesting these sites as effective targets for potential influenza antiviral development.

PubMed: 35017564
DOI: 10.1038/s41467-021-27950-w

実験手法

ELECTRON MICROSCOPY (4.07 Å)