The RIG-I-like Receptor LGP2 Recognizes the Termini of Double-stranded RNA
0301 basic medicine
0303 health sciences
Interferon-Induced Helicase, IFIH1
Receptors, Retinoic Acid
Crystallography, X-Ray
Protein Structure, Tertiary
3. Good health
DEAD-box RNA Helicases
Structure-Activity Relationship
03 medical and health sciences
Mutation
Humans
RNA Helicases
Protein Binding
RNA, Double-Stranded
Signal Transduction
DOI:
10.1074/jbc.m900818200
Publication Date:
2009-03-12T01:34:25Z
AUTHORS (7)
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.
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