National Natural Science Foundation of China (NSFC)
81971538
中国
引用
ジャーナル: Immunity / 年: 2021 タイトル: Ordered assembly of the cytosolic RNA-sensing MDA5-MAVS signaling complex via binding to unanchored K63-linked poly-ubiquitin chains. 著者: Bin Song / Yun Chen / Xin Liu / Fei Yuan / Eddie Yong Jun Tan / Yixuan Lei / Ning Song / Yinqi Han / Bruce D Pascal / Patrick R Griffin / Cheng Luo / Bin Wu / Dahai Luo / Jie Zheng / 要旨: The RNA sensor MDA5 recruits the signaling adaptor MAVS to initiate type I interferon signaling and downstream antiviral responses, a process that requires K63-linked polyubiquitin chains. Here, we ...The RNA sensor MDA5 recruits the signaling adaptor MAVS to initiate type I interferon signaling and downstream antiviral responses, a process that requires K63-linked polyubiquitin chains. Here, we examined the mechanisms whereby K63-polyUb chain regulate MDA5 activation. Only long unanchored K63-polyUb (n ≥ 8) could mediate tetramerization of the caspase activation and recruitment domains of MDA5 (CARDs). Cryoelectron microscopy structures of a polyUb-bound CARDs tetramer and a polyUb-bound CARDs-CARD assembly revealed a tower-like formation, wherein eight Ubs tethered along the outer rim of the helical shell, bridging CARDs and CARD tetramers into proximity. ATP binding and hydrolysis promoted the stabilization of RNA-bound MDA5 prior to MAVS activation via allosteric effects on CARDs-polyUb complex. Abundant ATP prevented basal activation of apo MDA5. Our findings reveal the ordered assembly of a MDA5 signaling complex competent to recruit and activate MAVS and highlight differences with RIG-I in terms of CARD orientation and Ub sensing that suggest different abilities to induce antiviral responses.
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2021年10月13日
Data content type: Primary map / Data content type: Primary map / Provider: repository / タイプ: Initial release
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2021年10月13日
Data content type: Image / Data content type: Image / Provider: repository / タイプ: Initial release
改定 1.0
2021年10月13日
Data content type: Primary map / Data content type: Primary map / Provider: repository / タイプ: Initial release
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