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

Journal Article


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Abstract


  • 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.

Authors


  •   Stratmann, Sarah A. (external author)
  •   Morrone, Seamus R. (external author)
  •   van Oijen, Antoine M.
  •   Sohn, Jungsan (external author)

Publication Date


  • 2015

Published In


Citation


  • Stratmann, S. A., Morrone, S. R., van Oijen, A. M. & Sohn, J. (2015). The innate immune sensor IFI16 recognizes foreign DNA in the nucleus by scanning along the duplex. eLife, 4 e11721-1-e11721-13.

Scopus Eid


  • 2-s2.0-84988646188

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=4737&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/3714

Has Global Citation Frequency


Start Page


  • e11721-1

End Page


  • e11721-13

Volume


  • 4

Place Of Publication


  • United Kingdom

Abstract


  • 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.

Authors


  •   Stratmann, Sarah A. (external author)
  •   Morrone, Seamus R. (external author)
  •   van Oijen, Antoine M.
  •   Sohn, Jungsan (external author)

Publication Date


  • 2015

Published In


Citation


  • Stratmann, S. A., Morrone, S. R., van Oijen, A. M. & Sohn, J. (2015). The innate immune sensor IFI16 recognizes foreign DNA in the nucleus by scanning along the duplex. eLife, 4 e11721-1-e11721-13.

Scopus Eid


  • 2-s2.0-84988646188

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=4737&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/3714

Has Global Citation Frequency


Start Page


  • e11721-1

End Page


  • e11721-13

Volume


  • 4

Place Of Publication


  • United Kingdom