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-Structure paper
タイトル | Molecular imprinting as a signal-activation mechanism of the viral RNA sensor RIG-I. |
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ジャーナル・号・ページ | Mol Cell, Vol. 55, Issue 4, Page 511-523, Year 2014 |
掲載日 | 2014年8月21日 |
著者 | Bin Wu / Alys Peisley / David Tetrault / Zongli Li / Edward H Egelman / Katharine E Magor / Thomas Walz / Pawel A Penczek / Sun Hur / |
PubMed 要旨 | RIG-I activates interferon signaling pathways by promoting filament formation of the adaptor molecule, MAVS. Assembly of the MAVS filament is mediated by its CARD domain (CARD(MAVS)), and requires ...RIG-I activates interferon signaling pathways by promoting filament formation of the adaptor molecule, MAVS. Assembly of the MAVS filament is mediated by its CARD domain (CARD(MAVS)), and requires its interaction with the tandem CARDs of RIG-I (2CARD(RIG-I)). However, the precise nature of the interaction between 2CARD(RIG-I) and CARD(MAVS), and how this interaction leads to CARD(MAVS) filament assembly, has been unclear. Here we report a 3.6 Å electron microscopy structure of the CARD(MAVS) filament and a 3.4 Å crystal structure of the 2CARD(RIG-I):CARD(MAVS) complex, representing 2CARD(RIG-I) "caught in the act" of nucleating the CARD(MAVS) filament. These structures, together with functional analyses, show that 2CARD(RIG-I) acts as a template for the CARD(MAVS) filament assembly, by forming a helical tetrameric structure and recruiting CARD(MAVS) along its helical trajectory. Our work thus reveals that signal activation by RIG-I occurs by imprinting its helical assembly architecture on MAVS, a previously uncharacterized mechanism of signal transmission. |
リンク | Mol Cell / PubMed:25018021 / PubMed Central |
手法 | EM (らせん対称) / X線回折 |
解像度 | 3.4 - 3.64 Å |
構造データ | EMDB-5922: EMDB-5925: 3.6 Angstrom resolution MAVS filament generated from helical reconstruction, truncated map PDB-4p4h: |
由来 |
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キーワード | IMMUNE SYSTEM / CARD / MAVS / innate immunity / RIG-I / MDA5 / spontaneous filament formation / seeded filament formation / SIGNALING PROTEIN / signaling complex |