The RIG-I-like Receptor LGP2 Recognizes the Termini of Double-stranded RNA

• DOI: 10.1074/jbc.m900818200
• Publication Date: 2009-03-12T01:34:25Z
• Authors: Xiaojun Li; C.T. Ranjith-Kumar; Monica T. Brooks; S. Dharmaiah; Andrew B. Herr; Cheng Kao; Pingwei Li
• Keywords: RIG-I

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