SARS-CoV-1 M protein interacts with TRAF3

Stable Identifier
R-HSA-9685162
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Human SARS coronavirus
Compartment
ReviewStatus
5/5
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Severe acute respiratory syndrome coronavirus type 1 (SARS-CoV-1) M protein is a glycosylated structural protein with three transmembrane (TM) domains. M protein predominantly localizes to the Golgi complex and is essential for the assembly of viral particles. SARS-CoV-1 M protein was found to suppress production of type I IFNs in human embryonic kidney 293 cells (HEK293 cells) expressing RIG-I (DDX58), MDA5 (IFIH1), TRAF3, TBK1 and IKKε (IKBKE) proteins (Siu KL et al. 2009; 2014). IFN antagonism was mediated by N-terminal TM1 domain of SARS-CoV-1 M protein (amino acids 1–38), which targets M protein to the Golgi complex (Siu KL et al. 2014). Co-immunoprecipitation analysis revealed that TM1 of M protein interacted with TRAF3, RIG-I (DDX58), TBK1 and IKBKE (Siu KL et al. 2014) in HEK293 expressing tagged proteins (Siu KL et al. 2014). SARS-CoV-1 M protein is thought to prevent the formation of the TRAF3:TANK:TBK1/IKBKE complex and thereby inhibits TBK1/IKBKE-dependent activation of IRF3/IRF7 transcription factors (Siu KL et al. 2009; 2014). The Reactome event shows binding of SARS-CoV-1 M protein to TRAF3. This binding prevents TRAF3 from interacting with downstream effectors TANK, TBK1 and IKBKE (IKKε). However, it remains to be clarified how the Golgi-associated M protein might contribute to the suppression of IRF3/IRF7 activation under the DDX58:MAVS antiviral signaling axis.
Literature References
PubMed ID Title Journal Year
19380580 Severe acute respiratory syndrome coronavirus M protein inhibits type I interferon production by impeding the formation of TRAF3.TANK.TBK1/IKKepsilon complex

Siu, KL, Kok, KH, Ng, MH, Poon, VK, Yuen, KY, Zheng, BJ, Jin, DY

J. Biol. Chem. 2009
24509444 Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain

Siu, KL, Chan, CP, Kok, KH, Chiu-Yat Woo, P, Jin, DY

Cell. Mol. Immunol. 2014
Participants
Participates
Disease
Name Identifier Synonyms
severe acute respiratory syndrome DOID:2945 SARS-CoV infection, SARS
Cross References
Mondo
Authored
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