7VH3

Cryo-EM structure of Machupo virus polymerase L

Summary for 7VH3

• Entry DOI: 10.2210/pdb7vh3/pdb
• EMDB information: 31975 31983 31984 31985
• Descriptor: RNA-directed RNA polymerase L (1 entity in total)
• Functional Keywords: polymerase, viral protein
• Biological source: Machupo virus (MACV)
• Total number of polymer chains: 1
• Total formula weight: 253456.34

Authors

Ma, J.,Zhang, S.,Zhang, X. (deposition date: 2021-09-20, release date: 2021-09-29, Last modification date: 2024-10-16)

Primary citation

Ma, J.,Zhang, S.,Zhang, X.
Structure of Machupo virus polymerase in complex with matrix protein Z.
Nat Commun, 12:6163-6163, 2021

PubMed Abstract: 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.

PubMed: 34697302
DOI: 10.1038/s41467-021-26432-3

Experimental method

ELECTRON MICROSCOPY (3.6 Å)