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TitleStructure of Machupo virus polymerase in complex with matrix protein Z.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 6163, Year 2021
Publish dateOct 25, 2021
AuthorsJun Ma / Shuangyue Zhang / Xinzheng Zhang /
PubMed AbstractThe 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 ...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.
External linksNat Commun / PubMed:34697302 / PubMed Central
MethodsEM (single particle)
Resolution3.6 - 5.1 Å
Structure data

31975

7vgq

EMDB-31975, PDB-7vgq:
Cryo-EM structure of Machupo virus polymerase L in complex with matrix protein Z
Method: EM (single particle) / Resolution: 4.0 Å

31983

7vh1

EMDB-31983, PDB-7vh1:
Cryo-EM structure of Machupo virus dimeric L-Z complex
Method: EM (single particle) / Resolution: 4.2 Å

31984

7vh2

EMDB-31984, PDB-7vh2:
Cryo-EM structure of Machupo virus dimeric polymerase L
Method: EM (single particle) / Resolution: 5.1 Å

31985

7vh3

EMDB-31985, PDB-7vh3:
Cryo-EM structure of Machupo virus polymerase L
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • Machupo mammarenavirus
  • machupo virus
  • escherichia coli (strain k12) (bacteria)
KeywordsVIRAL PROTEIN / Polymerase / matrix protein / complex

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