Cryo-EM structure of Machupo virus polymerase L in complex with matrix protein ZCryo-EM structure of Machupo virus polymerase L in complex with matrix protein Z

Structural highlights

7vgq is a 2 chain structure with sequence from Escherichia coli K-12 and Mammarenavirus machupoense. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 4Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

L_MACHU 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.

Publication Abstract from PubMed

The Arenaviridae family includes several viruses that cause severe human hemorrhagic fevers with high mortality, with no effective countermeasures currently available. The arenavirus multi-domain L protein is involved in viral transcription and replication and represents a promising target for antiviral drugs. The arenavirus matrix protein Z is a small multi-functional protein that inhibits the activities of the L protein. Here we report the structure of Machupo virus L protein in complex with Z determined by cryo-electron microscopy. The Z protein acts as a staple and binds the L protein with 1:1 stoichiometry at the intersection between the PA-C-like region, RNA-dependent RNA polymerase and PB2-N-like region. Binding of the Z protein may lock the multiple domains of L into a fixed arrangement leading to loss of catalytic activity. These results further our understanding of the inhibitory mechanism of arenavirus replication machinery and provide a novel perspective to develop antiviral drugs.

Structure of Machupo virus polymerase in complex with matrix protein Z.,Ma J, Zhang S, Zhang X Nat Commun. 2021 Oct 25;12(1):6163. doi: 10.1038/s41467-021-26432-3. PMID:34697302[1]

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

See Also

References

  1. Ma J, Zhang S, Zhang X. Structure of Machupo virus polymerase in complex with matrix protein Z. Nat Commun. 2021 Oct 25;12(1):6163. doi: 10.1038/s41467-021-26432-3. PMID:34697302 doi:http://dx.doi.org/10.1038/s41467-021-26432-3

7vgq, resolution 4.00Å

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