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TitleMolecular imprinting as a signal-activation mechanism of the viral RNA sensor RIG-I.
Journal, issue, pagesMol Cell, Vol. 55, Issue 4, Page 511-523, Year 2014
Publish dateAug 21, 2014
AuthorsBin Wu / Alys Peisley / David Tetrault / Zongli Li / Edward H Egelman / Katharine E Magor / Thomas Walz / Pawel A Penczek / Sun Hur /
PubMed AbstractRIG-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.
External linksMol Cell / PubMed:25018021 / PubMed Central
MethodsEM (helical sym.) / X-ray diffraction
Resolution3.4 - 3.64 Å
Structure data

EMDB-5922:
3.6 Angstrom resolution MAVS filament generated from helical reconstruction
Method: EM (helical sym.) / Resolution: 3.64 Å

5925

3j6j

EMDB-5925: 3.6 Angstrom resolution MAVS filament generated from helical reconstruction, truncated map
PDB-3j6j: 3.6 Angstrom resolution MAVS filament generated from helical reconstruction
Method: EM (helical sym.) / Resolution: 3.64 Å

PDB-4p4h:
Caught-in-action signaling complex of RIG-I 2CARD domain and MAVS CARD domain
Method: X-RAY DIFFRACTION / Resolution: 3.4 Å

Source
  • homo sapiens (human)
KeywordsIMMUNE SYSTEM / CARD / MAVS / innate immunity / RIG-I / MDA5 / spontaneous filament formation / seeded filament formation / SIGNALING PROTEIN / signaling complex

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