Cooperative assembly of IFI16 filaments on dsDNA provides insights into host defense strategy.

ABSTRACT: Whether host DNA receptors have any capacity to distinguish self from nonself at the molecular level is an outstanding question in the innate immunity of mammals. Here, by using quantitative assays and electron microscopy, we show that cooperatively assembling into filaments on dsDNA may serve as an integral mechanism by which human IFN-inducible protein-16 (IFI16) engages foreign DNA. IFI16 is essential for defense against a number of different pathogens, and its aberrant activity is also implicated in several autoimmune disorders, such as Sjögren syndrome. IFI16 cooperatively binds dsDNA in a length-dependent manner and clusters into distinct protein filaments even in the presence of excess dsDNA. Consequently, the assembled IFI16⋅dsDNA oligomers are clearly different from the convention

SUBMITTER: Morrone SR 

PROVIDER: S-EPMC3890864 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature