Molecular Imprinting as a Signal-Activation Mechanism of the Viral RNA Sensor RIG-I
| Autor: | Thomas Walz, Bin Wu, Zongli Li, Pawel A. Penczek, Edward H. Egelman, Katharine E. Magor, Sun Hur, Alys Peisley, David G. Tetrault |
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| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular Protein Conformation viruses chemical and pharmacologic phenomena Biology DEAD-box RNA Helicases Molecular Imprinting Protein filament Protein structure Viral rna Protein Structure Quaternary Molecular Biology Adaptor Proteins Signal Transducing Genetics Binding Sites RIG-I virus diseases Signal transducing adaptor protein Cell Biology biochemical phenomena metabolism and nutrition Protein Structure Tertiary Microscopy Electron Biophysics CARD domain RNA Viral biological phenomena cell phenomena and immunity Molecular imprinting Adaptor molecule |
| Zdroj: | Molecular Cell. 55(4):511-523 |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2014.06.010 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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