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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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.