Structural highlights
Function
[V_SV5] Blocks host interferon signaling. Induces the ubiquitination and subsequent proteasome-mediated degradation of host STAT1. Acts as an adapter, linking host DDB1-Cullin 4 to STAT2/STAT1 complex. There is an absolute requirement of STAT2 in STAT1 degradation, as V binds specifically to STAT2. Might act as a chaperone keeping the viral nucleoprotein soluble. Interacts with host IFIH1/MDA5 to block its activity in the transduction pathway which leads to the activation of IFN-beta promoter, thus protecting the virus against cell antiviral state.[1]
Publication Abstract from PubMed
The RIG-I like receptor MDA5 senses cytoplasmic viral RNA and activates antiviral innate immunity. To reveal how paramyxoviruses counteract this response, we determined the crystal structure of the MDA5 ATP-hydrolysis domain in complex with the viral inhibitor V protein. The V protein unfolded the ATPase domain of MDA5 via a beta-hairpin motif and recognized a structural motif of MDA5 that is normally buried in the conserved helicase fold. This leads to disruption of the MDA5 ATP-hydrolysis site and prevention of RNA bound MDA5 filament formation. The structure explains why V proteins inactivate MDA5, but not RIG-I, and mutating only two amino acids in RIG-I induces robust V protein binding. Our results suggest an inhibition mechanism of RLR signalosome formation by unfolding of receptor and inhibitor.
Paramyxovirus V Proteins Disrupt the Fold of the RNA Sensor MDA5 to Inhibit Antiviral Signaling.,Motz C, Schuhmann KM, Kirchhofer A, Moldt M, Witte G, Conzelmann KK, Hopfner KP Science. 2013 Jan 17. PMID:23328395[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lin Y, Horvath F, Aligo JA, Wilson R, He B. The role of simian virus 5 V protein on viral RNA synthesis. Virology. 2005 Aug 1;338(2):270-80. PMID:15950997 doi:http://dx.doi.org/S0042-6822(05)00287-4
- ↑ Motz C, Schuhmann KM, Kirchhofer A, Moldt M, Witte G, Conzelmann KK, Hopfner KP. Paramyxovirus V Proteins Disrupt the Fold of the RNA Sensor MDA5 to Inhibit Antiviral Signaling. Science. 2013 Jan 17. PMID:23328395 doi:http://dx.doi.org/10.1126/science.1230949
