7OCH

Apo-structure of Lassa virus L protein (well-resolved polymerase core) [APO-CORE]

7OCH の概要

• エントリーDOI: 10.2210/pdb7och/pdb
• EMDBエントリー: 12807
• 分子名称: RNA-directed RNA polymerase L, ZINC ION, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: lassa virus rna-dependent rna polymerase viral rna, viral protein
• 由来する生物種: Lassa mammarenavirus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 253746.65

構造登録者

Kouba, T.,Vogel, D.,Thorkelsson, S.,Quemin, E.,Williams, H.M.,Milewski, M.,Busch, C.,Gunther, S.,Grunewald, K.,Rosenthal, M.,Cusack, S. (登録日: 2021-04-26, 公開日: 2021-12-01, 最終更新日: 2025-07-09)

主引用文献

Kouba, T.,Vogel, D.,Thorkelsson, S.R.,Quemin, E.R.J.,Williams, H.M.,Milewski, M.,Busch, C.,Gunther, S.,Grunewald, K.,Rosenthal, M.,Cusack, S.
Conformational changes in Lassa virus L protein associated with promoter binding and RNA synthesis activity.
Nat Commun, 12:7018-7018, 2021

PubMed Abstract: Lassa virus is endemic in West Africa and can cause severe hemorrhagic fever. The viral L protein transcribes and replicates the RNA genome via its RNA-dependent RNA polymerase activity. Here, we present nine cryo-EM structures of the L protein in the apo-, promoter-bound pre-initiation and active RNA synthesis states. We characterize distinct binding pockets for the conserved 3' and 5' promoter RNAs and show how full-promoter binding induces a distinct pre-initiation conformation. In the apo- and early elongation states, the endonuclease is inhibited by two distinct L protein peptides, whereas in the pre-initiation state it is uninhibited. In the early elongation state, a template-product duplex is bound in the active site cavity together with an incoming non-hydrolysable nucleotide and the full C-terminal region of the L protein, including the putative cap-binding domain, is well-ordered. These data advance our mechanistic understanding of how this flexible and multifunctional molecular machine is activated.

PubMed: 34857749
DOI: 10.1038/s41467-021-27305-5

実験手法

ELECTRON MICROSCOPY (3.14 Å)