2026-01-20 東京科学大学
図1. LGP2:MDA5:RNA複合体のクライオ電子顕微鏡構造
<関連情報>
- https://www.isct.ac.jp/ja/news/mxe4m8cmtlpm
- https://www.isct.ac.jp/plugins/cms/component_download_file.php?type=2&pageId=&contentsId=1&contentsDataId=3081&prevId=&key=03d59585966c000b407ae7b8064507ff.pdf
- https://www.sciencedirect.com/science/article/abs/pii/S1097276525010172
LGP2によるMDA5の核形成とフィラメント形成の分子メカニズム Molecular mechanism of MDA5 nucleation and filament formation by LGP2
Nina Kurihara, Yukari Isayama, Jiayan Zhang, Takashi Yamashita, Kentaro Awaji, Yukiko Ito, Ayumi Yoshizaki, Takahisa Kouwaki , Hiroyuki Oshiumi , Hiroshi Nishimasu, Mikihiro Shibata, Osamu Nureki , Kazuki Kato
Molecular Cell Available online: 19 January 2026
DOI:https://doi.org/10.1016/j.molcel.2025.12.019
Highlights
- LGP2 enables MDA5 sensing of short dsRNAs to enhance antiviral immunity
- LGP2 binds dsRNA ends and translocates internally via ATP hydrolysis
- LGP2 nucleates MDA5 assembly on internal dsRNA stems via its capping loop
- LGP2:MDA5 microclusters promote robust MAVS-mediated signaling
Summary
LGP2, a RIG-I-like receptor, plays a crucial role in antiviral immunity by enhancing MDA5 activity against specific viral infections. Here, using biochemical assays, cryo-electron microscopy (cryo-EM), and high-speed atomic force microscopy, we reveal that LGP2 initially binds to the ends of double-stranded RNA (dsRNA) and subsequently translocates along the RNA via ATP hydrolysis. Our cryo-EM structure demonstrates that LGP2 forms filament-like assemblies with MDA5 along the internal region of dsRNA, promoting MDA5 filament nucleation. Additionally, LGP2 and MDA5 form short RNA filaments, which are further cross-bridged via caspase activation and recruitment domain (CARD)-CARD interactions, leading to the formation of filament microclusters. These microclusters, in turn, stimulate mitochondrial antiviral signaling (MAVS) filament formation. Our findings uncover a dynamic interplay between LGP2 and MDA5, revealing a previously unrecognized mechanism that enhances antiviral immune responses.
