Higher-order structures of ligand bound RIG-I and cGAS (A30(A24*))

• Subject Area: Biochemistry
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 369799452

The cytosolic receptors RIG-I and cGAS detect invading virus RNA or DNA. While RIG-I recognizes short (20-1000 bp) 5’-triphosphorylated double stranded(ds) RNA, cGAS detects either dsDNA longer than 40-60 bp or short Y-form dsDNA containing unpaired guanosines flanking short (12 to 20 bp) dsDNA (YSD). Upon ligand binding, RIG-I/cGAS form higher-order complexes that activate kinases. Quaternary complex structures of full-length RIG-I/cGAS with short ligands are elusive so far. Using cryo-EM, structure guided mutational analysis, immunological, biochemical and filament-elongation assays we aim at resolving the mechanism behind the activation of cGAS and RIG-I by YSD and short RNA ligands, respectively.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 237: Nucleic Acid Immunity
• Applicant Institution: Ludwig-Maximilians-Universität München
• Project Heads: Professor Dr. Matthias Geyer; Professor Dr. Martin Schlee