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- W4323037607 abstract "Upon sensing cytosolic- and/or viral double-stranded (ds)DNA, absent-in-melanoma-2 (AIM2)-like-receptors (ALRs) assemble into filamentous signaling platforms to initiate inflammatory responses. The versatile yet critical roles of ALRs in host innate defense are increasingly appreciated; however, the mechanisms by which AIM2 and its related IFI16 specifically recognize dsDNA over other nucleic acids remain poorly understood (i.e. single-stranded (ss)DNA, dsRNA, ssRNA and DNA:RNA hybrid). Here, we find that although AIM2 can interact with various nucleic acids, it preferentially binds to and assembles filaments faster on dsDNA in a duplex length-dependent manner. Moreover, AIM2 oligomers assembled on nucleic acids other than dsDNA not only display less ordered filamentous structures, but also fail to induce the polymerization of downstream ASC. Likewise, although showing broader nucleic acid selectivity than AIM2, IFI16 binds to and oligomerizes most readily on dsDNA in a duplex length-dependent manner. Nevertheless, IFI16 fails to form filaments on single-stranded nucleic acids and does not accelerate the polymerization of ASC regardless of bound nucleic acids. Together, we reveal that filament assembly is integral to nucleic acid distinction by ALRs." @default.
- W4323037607 created "2023-03-04" @default.
- W4323037607 creator A5004554901 @default.
- W4323037607 creator A5048612030 @default.
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- W4323037607 date "2023-03-02" @default.
- W4323037607 modified "2023-10-15" @default.
- W4323037607 title "Filament assembly underpins the double-stranded DNA specificity of AIM2-like receptors" @default.
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- W4323037607 doi "https://doi.org/10.1093/nar/gkad090" @default.
- W4323037607 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36864667" @default.
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