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A STING-based biosensor affords broad cyclic dinucleotide detection within single living eukaryotic cells.


ABSTRACT: Cyclic dinucleotides (CDNs) are second messengers conserved across all three domains of life. Within eukaryotes they mediate protective roles in innate immunity against malignant, viral, and bacterial disease, and exert pathological effects in autoimmune disorders. Despite their ubiquitous role in diverse biological contexts, CDN detection methods are limited. Here, using structure guided design of the murine STING CDN binding domain, we engineer a Förster resonance energy transfer (FRET) based biosensor deemed BioSTING. Recombinant BioSTING affords real-time detection of CDN synthase activity and inhibition. Expression of BioSTING in live human cells allows quantification of localized bacterial and eukaryotic CDN levels in single cells with low nanomolar sensitivity. These findings establ

SUBMITTER: Pollock AJ 

PROVIDER: S-EPMC7363834 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature