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Stimulation of Cytoplasmic DNA Sensing Pathways In Vitro and In Vivo
Published on: September 18, 2014
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STING cyclic dinucleotide sensing originated in bacteria.
Benjamin R Morehouse1,2, Apurva A Govande1,2, Adi Millman3
1Department of Microbiology, Harvard Medical School, Boston, MA, USA.
Nature
|September 3, 2020
Summary
The Stimulator of interferon genes (STING) pathway, crucial for immunity, has ancient origins in bacteria. Researchers discovered functional bacterial STING, revealing its conserved role in innate immunity against viruses and bacteria.
Area of Science:
- Immunology
- Structural Biology
- Evolutionary Biology
Background:
- Stimulator of interferon genes (STING) is a key receptor in human innate immunity, sensing cyclic dinucleotides during infections.
- Its unique structure has hindered understanding of its origins and cyclic dinucleotide signaling in mammals.
Purpose of the Study:
- To investigate the evolutionary origins and functional mechanisms of STING signaling.
- To elucidate the conserved signaling pathway involving STING in prokaryotes.
Main Methods:
- Crystal structure determination of bacterial STING homologues.
- Comparative structural analysis of bacterial and metazoan STING.
- Reconstruction of evolutionary events in STING acquisition.
Main Results:
- Identified functional STING homologues in prokaryotic defense islands with conserved activation mechanisms.
- Determined the structure of bacterial STING, revealing a minimal scaffold responding to cyclic di-GMP.
- Demonstrated how metazoan STING evolved for antiviral transcription regulation.
Conclusions:
- The cyclic GMP-AMP synthase (cGAS)-STING pathway is conserved in prokaryotes for defense against bacteriophages.
- Bacterial STING utilizes a conserved mechanism involving cyclic dinucleotide recognition and filament formation.
- Metazoan STING evolved from prokaryotic origins, adapting for sophisticated immune regulation.
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