4I1S

Melanoma differentiation associated protein-5 Helicase domain complex with inhibitor Non-structural protein V

Summary for 4I1S

• Entry DOI: 10.2210/pdb4i1s/pdb
• Descriptor: Melanoma differentiation associated protein-5, Non-structural protein V, ZINC ION, ... (4 entities in total)
• Functional Keywords: sf2-atpase, helicase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Sus scrofa (pigs,swine,wild boar); More
• Cellular location: Host cytoplasm : P11207
• Total number of polymer chains: 2
• Total formula weight: 34562.13

Authors

Motz, C.,Witte, G.,Hopfner, K.P. (deposition date: 2012-11-21, release date: 2013-01-30, Last modification date: 2024-11-06)

Primary citation

Motz, C.,Schuhmann, K.M.,Kirchhofer, A.,Moldt, M.,Witte, G.,Conzelmann, K.K.,Hopfner, K.P.
Paramyxovirus V proteins disrupt the fold of the RNA sensor MDA5 to inhibit antiviral signaling.
Science, 339:690-693, 2013

PubMed Abstract: The retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) melanoma differentiation-associated protein 5 (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 adenosine 5'-triphosphate (ATP)-hydrolysis domain in complex with the viral inhibitor V protein. The V protein unfolded the ATP-hydrolysis domain of MDA5 via a β-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.

PubMed: 23328395
DOI: 10.1126/science.1230949

Experimental method

X-RAY DIFFRACTION (2.293 Å)