7ELC

Structure of monomeric complex of MACV L bound to Z and 3'-vRNA

7ELC の概要

• エントリーDOI: 10.2210/pdb7elc/pdb
• EMDBエントリー: 31180
• 分子名称: RNA-directed RNA polymerase L, RING finger protein Z, 3'-vRNA promoter, ... (5 entities in total)
• 機能のキーワード: machupo virus, polymerase, z protein, replication regulation, viral protein-rna complex, viral protein/rna
• 由来する生物種: Machupo mammarenavirus (MACV); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 267462.55

構造登録者

Xu, X.,Peng, R.,Peng, Q.,Shi, Y. (登録日: 2021-04-09, 公開日: 2021-05-05, 最終更新日: 2024-10-23)

主引用文献

Xu, X.,Peng, R.,Peng, Q.,Wang, M.,Xu, Y.,Liu, S.,Tian, X.,Deng, H.,Tong, Y.,Hu, X.,Zhong, J.,Wang, P.,Qi, J.,Gao, G.F.,Shi, Y.
Cryo-EM structures of Lassa and Machupo virus polymerases complexed with cognate regulatory Z proteins identify targets for antivirals.
Nat Microbiol, 6:921-931, 2021

PubMed Abstract: Zoonotic arenaviruses can lead to life-threating diseases in humans. These viruses encode a large (L) polymerase that transcribes and replicates the viral genome. At the late stage of replication, the multifunctional Z protein interacts with the L polymerase to shut down RNA synthesis and initiate virion assembly. However, the mechanism by which the Z protein regulates the activity of L polymerase is unclear. Here, we used cryo-electron microscopy to resolve the structures of both Lassa and Machupo virus L polymerases in complex with their cognate Z proteins, and viral RNA, to 3.1-3.9 Å resolutions. These structures reveal that Z protein binding induces conformational changes in two catalytic motifs of the L polymerase, and restrains their conformational dynamics to inhibit RNA synthesis, which is supported by hydrogen-deuterium exchange mass spectrometry analysis. Importantly, we show, by in vitro polymerase reactions, that Z proteins of Lassa and Machupo viruses can cross-inhibit their L polymerases, albeit with decreased inhibition efficiencies. This cross-reactivity results from a highly conserved determinant motif at the contacting interface, but is affected by other variable auxiliary motifs due to the divergent evolution of Old World and New World arenaviruses. These findings could provide promising targets for developing broad-spectrum antiviral drugs.

PubMed: 34127846
DOI: 10.1038/s41564-021-00916-w

実験手法

ELECTRON MICROSCOPY (3.1 Å)