The RIG-I-like Receptor LGP2 Recognizes the Termini of Double-stranded RNA* Academic Article uri icon

abstract

  • The RIG-I-like receptors (RLRs), RIG-I and MDA5, recognize single-stranded RNA with 5' triphosphates and double-stranded RNA (dsRNA) to initiate innate antiviral immune responses. LGP2, a homolog of RIG-I and MDA5 that lacks signaling capability, regulates the signaling of the RLRs. To establish the structural basis of dsRNA recognition by the RLRs, we have determined the 2.0-A resolution crystal structure of human LGP2 C-terminal domain bound to an 8-bp dsRNA. Two LGP2 C-terminal domain molecules bind to the termini of dsRNA with minimal contacts between the protein molecules. Gel filtration chromatography and analytical ultracentrifugation demonstrated that LGP2 binds blunt-ended dsRNA of different lengths, forming complexes with 2:1 stoichiometry. dsRNA with protruding termini bind LGP2 and RIG-I weakly and do not stimulate the activation of RIG-I efficiently in cells. Surprisingly, full-length LGP2 containing mutations that abolish dsRNA binding retained the ability to inhibit RIG-I signaling.

altmetric score

  • 6

author list (cited authors)

  • Li, X., Ranjith-Kumar, C. T., Brooks, M. T., Dharmaiah, S., Herr, A. B., Kao, C., & Li, P.

citation count

  • 110

complete list of authors

  • Li, Xiaojun||Ranjith-Kumar, CT||Brooks, Monica T||Dharmaiah, S||Herr, Andrew B||Kao, Cheng||Li, Pingwei

publication date

  • May 2009