The C-Terminal Regulatory Domain Is the RNA 5`-Triphosphate Sensor of RIG-I

Molecular Cell, 2008, Vol. 29, 169-79 published on 01.02.2008
Molecular Cell; online article
The ATPase RIG-I senses viral RNAs that contain 5`triphosphates in the cytoplasm. It initiates a signaling cascade that activates innate immune response by interferon and cytokine production, providing essential antiviral protection for the host. The mode of RNA 50-triphosphate sensing by RIG-I remains elusive. We show that the C-terminal regulatory domain RD of RIG-I binds viral RNA in a 50-triphosphate-dependent manner and activates the RIG-I ATPase by RNAdependent dimerization. The crystal structure of RD reveals a zinc-binding domain that is structurally related to GDP/GTP exchange factors of Rab-like GTPases. The zinc coordination site is essential for RIG-I signaling and is also conserved in MDA5 and LGP2, suggesting related RD domains in all three enzymes. Structure-guided mutagenesis identifies a positively charged groove as likely 5`-triphosphate-binding site of RIG-I. This groove is distinct in MDA5 and LGP2, raising the possibility that RD confers ligand specificity.    

Campus Movie 2020


Campus Movie 2012

TU München
Helmholtz München
MPI of Neurobiology
MPI of Biochemistry