The innate immune sensor IFI16 recognizes foreign DNA in the nucleus by scanning along the duplex
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 nucleu...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-12-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/11721 |
| _version_ | 1828375576282398720 |
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| author | Sarah A Stratmann Seamus R Morrone Antoine M van Oijen Jungsan Sohn |
| author_facet | Sarah A Stratmann Seamus R Morrone Antoine M van Oijen Jungsan Sohn |
| author_sort | Sarah A Stratmann |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T07:49:20Z |
| format | Article |
| id | doaj.art-e7fcd62206834c138cd64fc4965072cc |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:49:20Z |
| publishDate | 2015-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-e7fcd62206834c138cd64fc4965072cc2022-12-22T02:05:15ZengeLife Sciences Publications LtdeLife2050-084X2015-12-01410.7554/eLife.11721The innate immune sensor IFI16 recognizes foreign DNA in the nucleus by scanning along the duplexSarah A Stratmann0Seamus R Morrone1Antoine M van Oijen2Jungsan Sohn3University of Groningen, Groningen, NetherlandsJohns Hopkins University School of Medicine, Baltimore, United StatesUniversity of Groningen, Groningen, Netherlands; University of Wollongong, Wollongong, AustraliaJohns Hopkins University School of Medicine, Baltimore, United StatesThe 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.https://elifesciences.org/articles/11721innate immunityhigher order assemblysingle-molecule biophysicskineticsself vs. nonself |
| spellingShingle | Sarah A Stratmann Seamus R Morrone Antoine M van Oijen Jungsan Sohn The innate immune sensor IFI16 recognizes foreign DNA in the nucleus by scanning along the duplex eLife innate immunity higher order assembly single-molecule biophysics kinetics self vs. nonself |
| title | The innate immune sensor IFI16 recognizes foreign DNA in the nucleus by scanning along the duplex |
| title_full | The innate immune sensor IFI16 recognizes foreign DNA in the nucleus by scanning along the duplex |
| title_fullStr | The innate immune sensor IFI16 recognizes foreign DNA in the nucleus by scanning along the duplex |
| title_full_unstemmed | The innate immune sensor IFI16 recognizes foreign DNA in the nucleus by scanning along the duplex |
| title_short | The innate immune sensor IFI16 recognizes foreign DNA in the nucleus by scanning along the duplex |
| title_sort | innate immune sensor ifi16 recognizes foreign dna in the nucleus by scanning along the duplex |
| topic | innate immunity higher order assembly single-molecule biophysics kinetics self vs. nonself |
| url | https://elifesciences.org/articles/11721 |
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