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Updated: Jun 26, 2026
11:44
Stimulation of Cytoplasmic DNA Sensing Pathways In Vitro and In Vivo
Published on: September 18, 2014
The mutational landscape of STING-induced immunity
Bing Zhang1, Pengbiao Xu1, Yu Meng1
1Global Health Institute, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland.
Nature
|June 24, 2026
Summary
Researchers mapped the function of thousands of STING protein variants to understand immune signaling. This reveals key molecular principles governing STING activity and its potential in various immune contexts.
Area of Science:
- Immunology
- Molecular Biology
- Structural Biology
Background:
- Stimulator of interferon genes (STING) is a crucial immune signaling protein involved in host defense, cancer, and inflammation.
- Understanding STING's sequence-function relationship is vital for its therapeutic targeting, but remains incomplete.
Purpose of the Study:
- To systematically map the sequence-function landscape of STING.
- To identify structural and functional determinants of STING activation and signaling.
- To explore the diversity of STING responses and regulatory principles.
Main Methods:
- Developed a massively parallel assay to profile thousands of single amino-acid STING variants.
- Utilized cryogenic-electron microscopy to determine structures of hyperactive STING variants.
- Analyzed mutational effects on STING's interaction with its ligand (2'3'-cGAMP) and downstream signaling pathways.
Main Results:
- Identified key sequence elements governing STING's immunostimulatory capacity and ligand recognition.
- Revealed new regulatory principles for STING conformational transitions using cryo-EM structures.
- Demonstrated that single amino-acid substitutions can alter STING sensitivity, decouple signaling pathways, and impact immune responses.
Conclusions:
- Defined molecular principles that tune STING activity and its functional potential.
- Highlighted the clinical and evolutionary relevance of natural STING variants.
- Provided a comprehensive map of STING's functional landscape for immune contexts.
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