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Cyclic di-GMP Sensing via the Innate Immune Signaling Protein STING
- Source :
- Molecular Cell. 46(6):735-745
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- Detection of foreign materials is the first step of successful immune responses. Stimulator of interferon genes (STING) was shown to directly bind cyclic diguanylate monophosphate (c-di-GMP), a bacterial second messenger, and to elicit strong interferon responses. Here we elucidate the structural features of the cytosolic c-di-GMP binding domain (CBD) of STING and its complex with c-di-GMP. The CBD exhibits an α + β fold and is a dimer in the crystal and in solution. Surprisingly, one c-di-GMP molecule binds to the central crevice of a STING dimer, using a series of stacking and hydrogen bonding interactions. We show that STING is autoinhibited by an intramolecular interaction between the CBD and the C-terminal tail (CTT) and that c-di-GMP releases STING from this autoinhibition by displacing the CTT. The structures provide a remarkable example of pathogen-host interactions in which a unique microbial molecule directly engages the innate immune system.
- Subjects :
- Cyclic di-GMP
Molecular Sequence Data
Plasma protein binding
Biology
Article
chemistry.chemical_compound
Protein structure
Humans
Amino Acid Sequence
Cyclic GMP
Molecular Biology
Binding Sites
Cyclic GMP-AMP synthase
Membrane Proteins
Hydrogen Bonding
Cell Biology
Immunity, Innate
eye diseases
Protein Structure, Tertiary
Sting
Biochemistry
chemistry
Stimulator of interferon genes
Second messenger system
Biophysics
Dimerization
Signal Transduction
Binding domain
Subjects
Details
- ISSN :
- 10972765
- Volume :
- 46
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Molecular Cell
- Accession number :
- edsair.doi.dedup.....0ae602c0821b09ef45faba50958eba13
- Full Text :
- https://doi.org/10.1016/j.molcel.2012.05.029