7OEA

Lassa virus L protein bound to 3' promoter RNA (well-resolved polymerase core) [3END-CORE]

Summary for 7OEA

• Entry DOI: 10.2210/pdb7oea/pdb
• Related: 7OCH
• EMDB information: 12862
• Descriptor: RNA-directed RNA polymerase L, 3' vRNA, ZINC ION, ... (5 entities in total)
• Functional Keywords: lassa virus rna-dependent rna polymerase viral rna, viral protein
• Biological source: Lassa mammarenavirus; More
• Total number of polymer chains: 2
• Total formula weight: 258860.73

Authors

Kouba, T.,Vogel, D.,Thorkelsson, S.,Quemin, E.,Williams, H.M.,Milewski, M.,Busch, C.,Gunther, S.,Grunewald, K.,Rosenthal, M.,Cusack, S. (deposition date: 2021-05-02, release date: 2021-12-01, Last modification date: 2025-07-09)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (2.7 Å)