MDA5-MAVS antiviral pathway activation mechanism revealed

Recently, the team of Zheng Jie, a researcher at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, revealed the K63-polyUb-mediated MDA5-MAVS antiviral signaling pathway assembly program and activation mechanism
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MDA5 is a heterologous RNA monitoring protein in cells, which can identify endogenous alu RNA and double-stranded RNA released by mitochondria without ADAR editing in autoimmune diseases
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Previous studies have found that short-chain K63-polyUb can effectively promote the oligomerization of RIG-ICARDs through covalent anchoring and non-covalent anchoring
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In this study, the researchers found that the long-chain, non-anchored K63-polyUb is similar to a "molecular bridge" through biological macromolecule hydrogen-deuterium exchange mass spectrometry and cryo-electron microscopy, which promotes the assembly of MDA5CARDs tetramers and makes them form An excited conformation to recruit downstream MAVSCARD to further promote the oligomerization and activation of MAVSCARD
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This study fills up the gaps in the research on MDA5 pathway activation and signal transduction, and further reveals the immunological function of long-chain, non-anchored K63-polyUb as an endogenous agonist in the cell, and in order to understand the molecular diversity of ubiquitin in anti-RNA The role of viral innate immune signal transduction and regulation provides new clues
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Song Bin, a postdoctoral fellow at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, and Chen Yun, a postdoctoral fellow at the National Institutes of Health, are the first authors of the paper, and Zheng Jie is the corresponding author of the paper
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Related paper information: https://doi.