The Thermodynamic Basis for Viral RNA Detection by the RIG-I Innate Immune Sensor |
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| Authors: | Adriana Vela Olga Fedorova Steve C Ding Anna Marie Pyle |
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| Institution: | From the Departments of ‡Molecular Biophysics and Biochemistry, ;§Molecular, Cellular, and Developmental Biology, and ;**Chemistry, Yale University, New Haven, Connecticut 06520, ;the ¶Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, and ;the ‖Burnham Institute for Medical Research, La Jolla, California 92037 |
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| Abstract: | 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. |
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| Keywords: | ATPases Interferon RNA Helicase RNA-Protein Interaction Viral Immunology RNA Triphosphate |
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