Journal
MOLECULAR CELL
Volume 76, Issue 2, Pages 243-254Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2019.09.023
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Funding
- NIAID NIH HHS [R01 AI111784, DP1 AI152074] Funding Source: Medline
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Self versus non-self discrimination by innate immune sensors is critical for mounting effective immune responses against pathogens while avoiding harmful auto-inflammatory reactions against the host. Foreign DNA and RNA sensors must discriminate between self versus non-self nucleic acids, despite their shared building blocks and similar physicochemical properties. Recent structural and biochemical studies suggest that multiple steps of filament-like assembly are required for the functions of several nucleic acid sensors. Here, we discuss ligand discrimination and oligomerization of RIG-I-like receptors, AIM2-like receptors, and cGAS. We discuss how filament-like assembly allows for robust and accurate discrimination of self versus non-self nucleic acids and how these assemblies enable sensing of multiple distinct features in foreign nucleic acids, including structure, length, and modifications. We also discuss how individual receptors differ in their assembly and disassembly mechanisms and how these differences contribute to the diversity in nucleic acid specificity and pathogen detection strategies.
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