Helical antimicrobial peptides assemble into protofibril scaffolds that present ordered dsDNA to TLR9
| العنوان: | Helical antimicrobial peptides assemble into protofibril scaffolds that present ordered dsDNA to TLR9 |
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| المؤلفون: | Lee, Ernest Y., Zhang, Changsheng, Di Domizio, Jeremy, Jin, Fan, Connell, Will, Hung, Mandy, Malkoff, Nicolas, Veksler, Veronica, Gilliet, Michel, Ren, Pengyu, Wong, Gerard C. L. |
| سنة النشر: | 2023 |
| المجموعة: | SciTec Connect (Office of Scientific and Technical Information - OSTI, U.S. Department of Energy) |
| مصطلحات موضوعية: | 59 BASIC BIOLOGICAL SCIENCES |
| الوصف: | Amphiphilicity in α-helical antimicrobial peptides (AMPs) is recognized as a signature of potential membrane activity. Some AMPs are also strongly immunomodulatory: LL37-DNA complexes potently amplify Toll-like receptor 9 (TLR9) activation in immune cells and exacerbate autoimmune diseases. The rules governing this proinflammatory activity of AMPs are unknown. Here we examine the supramolecular structures formed between DNA and three prototypical AMPs using small angle X-ray scattering and molecular modeling. We correlate these structures to their ability to activate TLR9 and show that a key criterion is the AMP’s ability to assemble into superhelical protofibril scaffolds. These structures enforce spatially-periodic DNA organization in nanocrystalline immunocomplexes that trigger strong recognition by TLR9, which is conventionally known to bind single DNA ligands. We demonstrate that we can “knock in” this ability for TLR9 amplification in membrane-active AMP mutants, which suggests the existence of tradeoffs between membrane permeating activity and immunomodulatory activity in AMP sequences. |
| نوع الوثيقة: | other/unknown material |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | http://www.osti.gov/servlets/purl/1624136Test; https://www.osti.gov/biblio/1624136Test; https://doi.org/10.1038/s41467-019-08868-wTest |
| DOI: | 10.1038/s41467-019-08868-w |
| الإتاحة: | https://doi.org/10.1038/s41467-019-08868-wTest http://www.osti.gov/servlets/purl/1624136Test https://www.osti.gov/biblio/1624136Test |
| رقم الانضمام: | edsbas.EABA662A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-019-08868-w |
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