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TitlecGAS facilitates sensing of extracellular cyclic dinucleotides to activate innate immunity.
Journal, issue, pagesEMBO Rep, Vol. 20, Issue 4, Year 2019
Publish dateMar 14, 2019
AuthorsHaipeng Liu / Pedro Moura-Alves / Gang Pei / Hans-Joachim Mollenkopf / Robert Hurwitz / Xiangyang Wu / Fei Wang / Siyu Liu / Mingtong Ma / Yiyan Fei / Chenggang Zhu / Anne-Britta Koehler / Dagmar Oberbeck-Mueller / Karin Hahnke / Marion Klemm / Ute Guhlich-Bornhof / Baoxue Ge / Anne Tuukkanen / Michael Kolbe / Anca Dorhoi / Stefan He Kaufmann /
PubMed AbstractCyclic dinucleotides (CDNs) are important second messenger molecules in prokaryotes and eukaryotes. Within host cells, cytosolic CDNs are detected by STING and alert the host by activating innate ...Cyclic dinucleotides (CDNs) are important second messenger molecules in prokaryotes and eukaryotes. Within host cells, cytosolic CDNs are detected by STING and alert the host by activating innate immunity characterized by type I interferon (IFN) responses. Extracellular bacteria and dying cells can release CDNs, but sensing of extracellular CDNs (eCDNs) by mammalian cells remains elusive. Here, we report that endocytosis facilitates internalization of eCDNs. The DNA sensor cGAS facilitates sensing of endocytosed CDNs, their perinuclear accumulation, and subsequent STING-dependent release of type I IFN Internalized CDNs bind cGAS directly, leading to its dimerization, and the formation of a cGAS/STING complex, which may activate downstream signaling. Thus, eCDNs comprise microbe- and danger-associated molecular patterns that contribute to host-microbe crosstalk during health and disease.
External linksEMBO Rep / PubMed:30872316 / PubMed Central
MethodsSAS (X-ray synchrotron)
Structure data

SASDEP9:
Cyclic GMP-AMP synthase (cGAS) (Cyclic GMP-AMP synthase, cGAS)
Method: SAXS/SANS

SASDEQ9:
Cyclic GMP-AMP synthase (cGAS) with cyclic guanosine monophosphate–adenosine monophosphate (2'3'-cGAMP)
Method: SAXS/SANS

Source
  • Homo sapiens (human)

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