The structural basis of 5' triphosphate double-stranded RNA recognition by RIG-I C-terminal domain. Academic Article uri icon

abstract

  • RIG-I is a cytosolic sensor of viral RNA that plays crucial roles in the induction of type I interferons. The C-terminal domain (CTD) of RIG-I is responsible for the recognition of viral RNA with 5' triphosphate (ppp). However, the mechanism of viral RNA recognition by RIG-I is still not fully understood. Here, we show that RIG-I CTD binds 5' ppp dsRNA or ssRNA, as well as blunt-ended dsRNA, and exhibits the highest affinity for 5' ppp dsRNA. Crystal structures of RIG-I CTD bound to 5' ppp dsRNA with GC- and AU-rich sequences revealed that RIG-I recognizes the termini of the dsRNA and interacts with the 5' ppp through extensive electrostatic interactions. Mutagenesis and RNA-binding studies demonstrated that similar binding surfaces are involved in the recognition of different forms of RNA. Mutations of key residues at the RNA-binding surface affected RIG-I signaling in cells.

published proceedings

  • Structure

altmetric score

  • 4

author list (cited authors)

  • Lu, C., Xu, H., Ranjith-Kumar, C. T., Brooks, M. T., Hou, T. Y., Hu, F., ... Li, P.

citation count

  • 176

complete list of authors

  • Lu, Cheng||Xu, Hengyu||Ranjith-Kumar, CT||Brooks, Monica T||Hou, Tim Y||Hu, Fuqu||Herr, Andrew B||Strong, Roland K||Kao, C Cheng||Li, Pingwei

publication date

  • January 2010