ATP-dependent one-dimensional movement maintains immune homeostasis by suppressing spontaneous MDA5 filament assembly
文献类型：期刊论文
| 作者 | Han, Xiao-Peng6; Rao, Ming6; Chang, Yu1,4,5; Zhu, Jun-Yan6; Cheng, Jun6; Li, Yu-Ting6; Qiong, Wu6; Ye, Si-Chao1; Zhang, Qiurong6; Zhang, Shao-Qing6 |
| 刊名 | CELL RESEARCH
 |
| 出版日期 | 2025-09-19 |
| 页码 | 13 |
| ISSN号 | 1001-0602 |
| DOI | 10.1038/s41422-025-01183-8 |
| 通讯作者 | Zhong, Jin(jzhong@ips.ac.cn) ; Liu, Jiaquan(liujiaquan@sibcb.ac.cn) |
| 英文摘要 | MDA5 is a RIG-I-like receptor (RLR) that recognizes viral double-stranded RNA (dsRNA) to initiate the innate immune response. Its activation requires filament formation along the dsRNA, which triggers the oligomerization of N-terminal caspase activation and recruitment domains. The ATPase activity of MDA5 is critical for immune homeostasis, likely by regulating filament assembly. However, the molecular basis underlying this process remains poorly understood. Here, we show that MDA5 operates as an ATP-hydrolysis-driven motor that translocates along dsRNA in a one-dimensional (1D) manner. Multiple MDA5 motors can cooperatively load onto a single dsRNA, but their movements rarely synchronize, inhibiting spontaneous filament formation and activation. LGP2, a key regulator of MDA5 signaling, recognizes MDA5 motors and blocks their movement, thereby promoting filament assembly through a translocation-directed mechanism. This unique assembly strategy underscores the role of 1D motion in higher-order protein oligomerization and reveals a novel mechanism for maintaining immune homeostasis. |
| WOS关键词 | ANTIVIRAL SIGNAL ACTIVATION ; DOUBLE-STRANDED-RNA ; RIG-I ; STRUCTURAL BASIS ; ADAPTER PROTEIN ; RECOGNITION ; LGP2 ; DIFFUSION ; BINDING ; DNA |
| 资助项目 | Chinese Academy of Sciences (CAS) ; Strategic Priority Research Program of the Chinese Academy of Science[XDB0570000] ; National Key R&D Program of China[2021YFA1300503] ; National Natural Science Foundation of China[32070944] |
| WOS研究方向 | Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:001574626200001 |
| 出版者 | SPRINGERNATURE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/321501]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zhong, Jin; Liu, Jiaquan |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Immun & Infect, Shanghai, Peoples R China 2.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Life Sci, Key Lab Syst Hlth Sci Zhejiang Prov, Hangzhou, Zhejiang, Peoples R China 3.New Cornerstone Sci Lab, Shenzhen, Guangdong, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Infect Dis Res Ctr, Shanghai, Peoples R China 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 6.Univ Chinese Acad Sci, Chinese Acad Sci,Shanghai Inst Biochem & Cell Biol, State Key Lab RNA Innovat Sci & Engn, CAS Ctr Excellence Mol Cell Sci,State Key Lab Mol, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Han, Xiao-Peng,Rao, Ming,Chang, Yu,et al. ATP-dependent one-dimensional movement maintains immune homeostasis by suppressing spontaneous MDA5 filament assembly[J]. CELL RESEARCH,2025:13. |
| APA | Han, Xiao-Peng.,Rao, Ming.,Chang, Yu.,Zhu, Jun-Yan.,Cheng, Jun.,...&Liu, Jiaquan.(2025).ATP-dependent one-dimensional movement maintains immune homeostasis by suppressing spontaneous MDA5 filament assembly.CELL RESEARCH,13. |
| MLA | Han, Xiao-Peng,et al."ATP-dependent one-dimensional movement maintains immune homeostasis by suppressing spontaneous MDA5 filament assembly".CELL RESEARCH (2025):13. |
入库方式： OAI收割
来源：上海药物研究所
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