3j6j
From Proteopedia
3.6 Angstrom resolution MAVS filament generated from helical reconstruction
Structural highlights
FunctionMAVS_HUMAN Required for innate immune defense against viruses. Acts downstream of DDX58/RIG-I and IFIH1/MDA5, which detect intracellular dsRNA produced during viral replication, to coordinate pathways leading to the activation of NF-kappa-B, IRF3 and IRF7, and to the subsequent induction of antiviral cytokines such as IFN-beta and RANTES (CCL5). Peroxisomal and mitochondrial MAVS act sequentially to create an antiviral cellular state. Upon viral infection, peroxisomal MAVS induces the rapid interferon-independent expression of defense factors that provide short-term protection, whereas mitochondrial MAVS activates an interferon-dependent signaling pathway with delayed kinetics, which amplifies and stabilizes the antiviral response. May activate the same pathways following detection of extracellular dsRNA by TLR3. May protect cells from apoptosis.[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedRIG-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 (CARDMAVS), and requires its interaction with the tandem CARDs of RIG-I (2CARDRIG-I). However, the precise nature of the interaction between 2CARDRIG-I and CARDMAVS, and how this interaction leads to CARDMAVS filament assembly, has been unclear. Here we report a 3.6 A electron microscopy structure of the CARDMAVS filament and a 3.4 A crystal structure of the 2CARDRIG-I:CARDMAVS complex, representing 2CARDRIG-I "caught in the act" of nucleating the CARDMAVS filament. These structures, together with functional analyses, show that 2CARDRIG-I acts as a template for the CARDMAVS filament assembly, by forming a helical tetrameric structure and recruiting CARDMAVS 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. Molecular Imprinting as a Signal-Activation Mechanism of the Viral RNA Sensor RIG-I.,Wu B, Peisley A, Tetrault D, Li Z, Egelman EH, Magor KE, Walz T, Penczek PA, Hur S Mol Cell. 2014 Jul 9. pii: S1097-2765(14)00492-4. doi:, 10.1016/j.molcel.2014.06.010. PMID:25018021[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Egelman E | Hur S | Li Z | Peisley A | Penczek P | Walz T | Wu B
