4P4H

Caught-in-action signaling complex of RIG-I 2CARD domain and MAVS CARD domain

Summary for 4P4H

• Entry DOI: 10.2210/pdb4p4h/pdb
• Descriptor: Probable ATP-dependent RNA helicase DDX58, Mitochondrial antiviral-signaling protein, Ubiquitin-60S ribosomal protein L40 (3 entities in total)
• Functional Keywords: signaling protein, signaling complex
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm: O95786; Mitochondrion outer membrane: Q7Z434; Ubiquitin: Cytoplasm . 60S ribosomal protein L40: Cytoplasm : P62987
• Total number of polymer chains: 21
• Total formula weight: 334392.81

Authors

Wu, B.,Hur, S. (deposition date: 2014-03-12, release date: 2014-07-30, Last modification date: 2023-12-27)

Primary citation

Wu, B.,Peisley, A.,Tetrault, D.,Li, Z.,Egelman, E.H.,Magor, K.E.,Walz, T.,Penczek, P.A.,Hur, S.
Molecular Imprinting as a Signal-Activation Mechanism of the Viral RNA Sensor RIG-I.
Mol.Cell, 55:511-523, 2014

PubMed Abstract: 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.

PubMed: 25018021
DOI: 10.1016/j.molcel.2014.06.010

Experimental method

X-RAY DIFFRACTION (3.4 Å)