viral dsRNA:IFIH1, viral dsRNA:K63polyUb-DDX58 bind MAVS

Stable Identifier
R-HSA-168909
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Influenza A virus, Human respiratory syncytial virus A, Rotavirus, Hepatitis C Virus, Measles virus
Compartment
cytosol, mitochondrial outer membrane
Synonyms
RIG-I/MDA5 interacts with IPS-1
ReviewStatus
5/5
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viral dsRNA:IFIH1, viral dsRNA:K63polyUb-DDX58 bind MAVS
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NLRC5 competes with IPS-1 for binding to the CARD domain of RIG-I/MDA5. NLRC5 specifically recognize the CARD domains of RIG-I/MDA5 when the CARD domains become accessible after viral infection, leading to dampened activation of IRF3.

NLRX1 is a member of nucleotide-binding domain and leucine-rich repeat containing (NLR) protein family. NLRX1 competes with RIG-I for IPS-1 interaction and has been identified as a negative regulator of RLR signaling. NLRX1 resides at the outer mitochondrial membrane where IPS-1 is located and this interaction is mediated by the CARD region of IPS-1 and a putative nucleotide-binding domain (NBD) of NLRX1. This interaction between NLRX1 and IPS-1 prevents the association between RIG-1/MDA5 and IPS-1.

Upon binding viral dsRNA, Probable ATP-dependent RNA helicase DDX58 (DDX58, RIG-I, RIG-1) and Interferon-induced helicase C domain-containing protein 1 (IFIH1, MDA5) recruit the downstream signal transducer Mitochondrial antiviral-signaling protein (MAVS, IPS-1). This mitochondria-bound adaptor has an N-terminal CARD-like domain (CLD) which associates with the CARD regions of DDX58 and IFIH1 to mediate induction of interferons.

Literature References
PubMed ID Title Journal Year
16153868 VISA is an adapter protein required for virus-triggered IFN-beta signaling

Xu, LG, Shu, HB, Han, KJ, Wang, YY, Zhai, Z, Li, LY

Mol Cell 2005
16125763 Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3

Seth, RB, Chen, ZJ, Sun, L, Ea, CK

Cell 2005
18307765 Crystal structure of human IPS-1/MAVS/VISA/Cardif caspase activation recruitment domain

Taylor, GL, Potter, JA, Randall, RE

BMC Struct Biol 2008
16127453 IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction

Takeuchi, O, Ishii, KJ, Kumar, H, Sato, S, Kawai, T, Takahashi, K, Kato, H, Coban, C

Nat Immunol 2005
Participants
Input
Output
Participates
as an event of
This event is regulated
Negatively by
Regulator
MAVS:NLRX1 [mitochondrial outer membrane] (Homo sapiens)
Active Unit
NLRX1 [mitochondrial outer membrane]
Regulator
viral dsRNA:IFIH1, 2xviral dsRNA:2xK63polyUb-DDX58:2xRNF135,TRIM25:2xATP:NLRC5 [cytosol] (Homo sapiens)
Active Unit
NLRC5 [cytosol]
Orthologous Events
Activated MDA5 binds IPS-1 (Gallus gallus)
Authored
Garapati, P V  (2010-08-02)
Reviewed
Akira, S  (2010-10-30)
Kawai, T  (2010-10-30)
Created
de Bono, B  (2005-11-22)
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