Structure of Machupo virus polymerase in complex with matrix protein Z
Jun Ma, Shuangyue Zhang & Xinzheng Zhang
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.
附件下载：
Structure of Machupo virus polymerase in complex with matrix protein Z, Nat Commun, 25 Oct 2021
Nature Communications, 25 October, 2021, DOI：https://doi.org/10.1038/s41467-021-26432-3
Structure of Machupo virus polymerase in complex with matrix protein Z
Jun Ma, Shuangyue Zhang & Xinzheng Zhang
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.
文章链接：https://www.nature.com/articles/s41467-021-26432-3