Structural highlights
Function
[A0A3S8NV63_9VIRU] RNA-dependent RNA polymerase which is responsible for replication and transcription of the viral RNA genome. During transcription, synthesizes 4 subgenomic RNAs, and assures their capping by a cap-snatching mechanism, in which cellular capped pre-mRNAs are used to generate primers for viral transcription. The 3'-end of subgenomic mRNAs molecules are heterogeneous and not polyadenylated. The replicase function is to direct synthesis of antigenomic and genomic RNA which are encapsidated and non capped. As a consequence of the use of the same enzyme for both transcription and replication, these mechanisms need to be well coordinated. These processes may be regulated by proteins N and Z in a dose-dependent manner.[HAMAP-Rule:MF_04086][PIRNR:PIRNR000836]
Publication Abstract from PubMed
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.
Conformational changes in Lassa virus L protein associated with promoter binding and RNA synthesis activity.,Kouba T, Vogel D, Thorkelsson SR, Quemin ERJ, Williams HM, Milewski M, Busch C, Gunther S, Grunewald K, Rosenthal M, Cusack S Nat Commun. 2021 Dec 2;12(1):7018. doi: 10.1038/s41467-021-27305-5. PMID:34857749[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kouba T, Vogel D, Thorkelsson SR, Quemin ERJ, Williams HM, 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. 2021 Dec 2;12(1):7018. doi: 10.1038/s41467-021-27305-5. PMID:34857749 doi:http://dx.doi.org/10.1038/s41467-021-27305-5
