The thermodynamic basis for viral RNA detection by the RIG-I innate immune sensor.
RIG-I is a cytoplasmic surveillance protein that contributes to the earliest stages of the vertebrate innate immune response. The protein specifically recognizes 5'-triphosphorylated RNA structures that are released into the cell by viruses, such as influenza and hepatitis C. To understand the energetic basis for viral RNA recognition by RIG-I, we studied the binding of RIG-I domain variants to a family of dsRNA ligands. Thermodynamic analysis revealed that the isolated RIG-I domains each make important contributions to affinity and that they interact using different strategies. Covalent linkage between the domains enhances RNA ligand specificity while reducing overall binding affinity, thereby providing a mechanism for discriminating virus from host RNA.
Department of Molecular Biophysics, Yale University, New Haven, Connecticut 06520, USA.
Adriana
A
Vela
Olga
O
Fedorova
Steve C
SC
Ding
Anna Marie
AM
Pyle
D006801:Humans; D007113:Immunity, Innate; D007700:Kinetics; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012330:RNA, Double-Stranded / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D013379:Substrate Specificity; D013816:Thermodynamics; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000378:metabolism*
D012330:RNA, Double-Stranded; D012367:RNA, Viral; C522809:RNF135 protein, human; D044767:Ubiquitin-Protein Ligases