SNAP output for PDB entry 7oea [SNAP web server]

PDB-id

7oea; SNAP-derived features in text and JSON formats; DNAproDB

Class

viral protein

Method

cryo-EM (2.7 Å)

Summary

Lassa virus l protein bound to 3' promoter RNA (well-resolved polymerase core) [3end-core]

Reference

Kouba T, Vogel D, Thorkelsson SR, Quemin ERJ, Williams HM, Milewski M, Busch C, Gunther S, Grunewald K, Rosenthal M, Cusack S (2021): "Conformational changes in Lassa virus L protein associated with promoter binding and RNA synthesis activity." Nat Commun, 12, 7018. doi: 10.1038/s41467-021-27305-5.

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.