7eju

From Proteopedia

Junin virus(JUNV) RNA polymerase L complexed with Z protein

Structural highlights

7eju is a 2 chain structure with sequence from Argentinian mammarenavirus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.5Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A0A0M4LRT1_JUNIN RNA-dependent RNA polymerase, which is responsible for the replication and transcription of the viral RNA genome using antigenomic RNA as an intermediate. During transcription, synthesizes subgenomic RNAs and assures their capping by a cap-snatching mechanism, which involves the endonuclease activity cleaving the host capped pre-mRNAs. These short capped RNAs are then used as 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

Junin virus (JUNV) causes Argentine hemorrhagic fever, a debilitating human disease of high mortality rates and a great risk to public health worldwide. Studying the L protein that replicates and transcribes the genome of JUNV, and its regulator Z protein should provide critical clues to identify therapeutic targets for disrupting the life cycle of JUNV. Here we report the 3.54 A cryo-EM structure of the JUNV L protein complexed with regulator Z protein. JUNV L structure reveals a conserved architecture containing signature motifs found in other L proteins. Structural analysis shows that L protein is regulated by binding of Z protein at the RNA product exit site. Based on these findings, we propose a model for the role of Z protein as a switch to turn on/off the viral RNA synthesis via its interaction with L protein. Our work unveils the mechanism of JUNV transcription, replication and regulation, which provides a framework for the rational design of antivirals for combating viral infections.

Structural basis for recognition and regulation of arenavirus polymerase L by Z protein.,Kang H, Cong J, Wang C, Ji W, Xin Y, Qian Y, Li X, Chen Y, Rao Z Nat Commun. 2021 Jul 5;12(1):4134. doi: 10.1038/s41467-021-24458-1. PMID:34226547^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kang H, Cong J, Wang C, Ji W, Xin Y, Qian Y, Li X, Chen Y, Rao Z. Structural basis for recognition and regulation of arenavirus polymerase L by Z protein. Nat Commun. 2021 Jul 5;12(1):4134. PMID:34226547 doi:10.1038/s41467-021-24458-1