Summary information and primary citation

6gpg; DSSR-derived features in text and JSON formats
antiviral protein
X-ray (2.894 Å)
Structure of the rig-i singleton-merten syndrome variant c268f
Lassig C, Lammens K, Gorenflos Lopez JL, Michalski S, Fettscher O, Hopfner KP (2018): "Unified mechanisms for self-RNA recognition by RIG-I Singleton-Merten syndrome variants." Elife, 7. doi: 10.7554/eLife.38958.
The innate immune sensor RIG-I detects cytosolic viral RNA and requires a conformational change caused by both ATP and RNA binding to induce an active signalling state and to trigger an immune response. Previously, we showed that ATP hydrolysis removes RIG-I from lower affinity self-RNAs (Lässig et al., 2015), revealing how ATP turnover helps RIG‑I distinguish viral from self-RNA and explaining why a mutation in a motif that slows down ATP hydrolysis causes the autoimmune disease Singleton-Merten syndrome (SMS). Here we show that a different, mechanistically unexplained SMS variant, C268F, localised in the ATP binding P-loop, can signal independently of ATP but still dependent on RNA. The structure in complex with dsRNA reveals that C268F helps induce a similar structural conformation in RIG-I than ATP. Our results uncover an unexpected mechanism how a mutation in a P-loop ATPase can induce a gain-of-function ATP state in the absence of ATP.

Cartoon-block schematics in six views (download the tarball)

PyMOL session file Download PDB file View in 3Dmol.js