Scientists have revealed the bio-chemical mechanisms by which Ubud2D3 and Ubud2N participate in RIG-I induced MAVS aggregation.

On May 4, the international academic journal Nature Communications published online the latest findings of the Research Group of Hou Fajian of the Institute of Biochemistry and Cell Biology of the Shanghai Institute of Life Sciences of the Chinese Academy of Sciences, Ue2D3 and Ube2N essential for RIG-I-mediated MAVS aggregation in antiviral innate immunity.
this work reveals the activation mechanism of the host cell pattern recognition subject molecule RIG-I, which provides a research foundation for a deeper understanding of the working mechanism of the RIG-I molecule.
Natural immunity is the body's first line of defense against pathogen infection, in which the signal transduction pathway mediated by the viral RNA subject RIG-I plays a key role in the immune response of cells responding to RNA virus infection.
previous studies have shown that RIG-I molecules release their own inhibitions and release their N-side CARD domain after identifying invading viral RNA molecules.
RIG-I's CARD domain interacts with mitochondrial protein MAVS and induces its aggregation (Cell, 2011), MAVS then de-inhibits itself to activate downstream transcription factors NF-B and IRF3 (Nat Commun, 2015), induce the expression of type I interferon, and ultimately remove the invading virus.
The study first established an in-body experimental system to study the necessary factors to induce MAVS aggregation, and found that Ubigatin Connective (E3) Riplet was necessary for RIG-I to identify viral RNA and activate MAVS, whereas the Ubigan connective enzyme TRIM25, which had previously been widely recognized in the field, was not directly involved in the bio-chemical process.
subsequently, through protein separation purification and mass spectrometry analysis, ubibin binding enzymes (E2) Ube2D3 and Ube2N, which assist Riplet in its antiviral function, were identified, and the two E2s were involved in Riplet's signal transducation process to activate RIG-I and induce MAVS aggregation.
further molecular mechanism studies have found that the Ube2D3-Riplet combination promotes K63-bit polypronistic modification of rig-I's CARD domain, while the Ube2N-Riplet combination promotes the synthesis of non-anchored K63-bit polypronin chains.
, K63-bit-linked polysuperin chains and RIG-I jointly induce the polyglomeration of MAVS and initiate a natural antiviral immune response.
Shubo lian read Shi Yuheng, Yuan Bofeng and Zhu Wenxuan as the co-first authors of this article, the co-authors are Beijing Institute of Life Sciences Ph.D. Chen Shi, research funding from the Fund Committee and the Chinese Academy of Sciences.
also received help and support from Professors Xia Generalping of Zhejiang University, Zhang Xiaodong of Wuhan University, Sun Shaocong, Professor of UT MD Anderson Cancer Center, Chen Degui, Wang Hongyan, Qiu Ying and Zhou Jinqiu of bio-chemical and cell institutes.
this research is also supported by the biochemistry and cell molecular biology technology platform and the cell analysis technology platform.
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