The innate immune sensor IFI16 recognizes foreign DNA in the nucleus by scanning along the duplex

• Published in: eLife Vol. 4; p. e11721
• Main Authors: Stratmann, Sarah A, Morrone, Seamus R, van Oijen, Antoine M, Sohn, Jungsan
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 16.12.2015; eLife Sciences Publications, Ltd
• Subjects: Biophysics and Structural Biology; Cell Nucleus - metabolism; DNA - immunology; DNA - metabolism; higher order assembly; Humans; Immunology; Innate immunity; kinetics; Nuclear Proteins - metabolism; Nucleosomes - metabolism; Phosphoproteins - metabolism; self vs. nonself; Short Report; single-molecule biophysics; self vs. nonself; single-molecule biophysics; innate immunity; higher order assembly; structural biology; none; kinetics; biophysics; immunology
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.11721

The ability to recognize foreign double-stranded (ds)DNA of pathogenic origin in the intracellular environment is an essential defense mechanism of the human innate immune system. However, the molecular mechanisms underlying distinction between foreign DNA and host genomic material inside the nucleus are not understood. By combining biochemical assays and single-molecule techniques, we show that the nuclear innate immune sensor IFI16 one-dimensionally tracks long stretches of exposed foreign dsDNA to assemble into supramolecular signaling platforms. We also demonstrate that nucleosomes represent barriers that prevent IFI16 from targeting host DNA by directly interfering with these one-dimensional movements. This unique scanning-assisted assembly mechanism allows IFI16 to distinguish friend from foe and assemble into oligomers efficiently and selectively on foreign DNA.