9IP2

Cryo-EM structure of the RNA-dependent RNA polymerase complex from Marburg virus

9IP2 の概要

• エントリーDOI: 10.2210/pdb9ip2/pdb
• EMDBエントリー: 60755
• 分子名称: RNA-directed RNA polymerase L,Maltose/maltodextrin-binding periplasmic protein, Maltose/maltodextrin-binding periplasmic protein,Polymerase cofactor VP35, ZINC ION (3 entities in total)
• 機能のキーワード: rna-dependent rna polymerase complex, viral protein
• 由来する生物種: Marburg virus - Musoke, Kenya, 1980; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 633552.91

構造登録者

Li, G.,Du, T.,Wang, J.,Wu, S.,Ru, H. (登録日: 2024-07-10, 公開日: 2025-04-09, 最終更新日: 2025-04-16)

主引用文献

Li, G.,Du, T.,Wang, J.,Jie, K.,Ren, Z.,Zhang, X.,Zhang, L.,Wu, S.,Ru, H.
Structural insights into the RNA-dependent RNA polymerase complexes from highly pathogenic Marburg and Ebola viruses.
Nat Commun, 16:3080-3080, 2025

PubMed Abstract: The Ebola and the Marburg viruses belong to the Filoviridae family, a group of filamentous, single-stranded, negative-sensed RNA viruses. Upon infection, uncontrolled propagation of the Ebola and the Marburg viruses causes severe hemorrhagic fevers with high mortality rates. The replication and transcription of viral genomes are mediated by a polymerase complex consisting of two proteins: L and its cofactor VP35. However, the molecular mechanism of filovirus RNA synthesis remains understudied due to the lack of high-resolution structures of L and VP35 complexes from these viruses. Here, we present the cryo-EM structures of the polymerase complexes for the Marburg virus and the Ebola virus at 2.7 Å and 3.1 Å resolutions respectively. Despite the similar assembly and overall structures between these two viruses, we identify virus-specific L-VP35 interactions. Our data show that intergeneric exchange of VP35 would diminish these interactions and prevent the formation of a functional chimeric polymerase complex between L protein and heterologous VP35. Additionally, we identify a contracted conformation of the Ebola virus polymerase structure, revealing the structural dynamics of the polymerase during RNA synthesis. These insights enhance our understanding of filovirus RNA synthesis mechanisms and may facilitate the development of antiviral drugs targeting filovirus polymerase.

PubMed: 40164610
DOI: 10.1038/s41467-025-58308-1

実験手法

ELECTRON MICROSCOPY (2.7 Å)