Back to Search
Start Over
Distinct Dynamic and Conformational Features of Human STING in Response to 2'3'-cGAMP and c-di-GMP
- Source :
- Chembiochem : a European journal of chemical biology. 20(14)
- Publication Year :
- 2019
-
Abstract
- The human stimulator of interferon genes protein (hSTING) can bind cyclic dinucleotides (CDNs) to activate the production of type I interferons and inflammatory cytokines. These CDNs can be either bacterial secondary messengers, 3'3'-CDNs, or endogenous 2'3'-cGAMP. cGAMP, with a unique 2'-5' bond, is the most potent activator of hSTING among all CDNs. However, current understanding of the molecular principles underlying the unique ability of 2'3'-cGAMP to potently activate hSTINGs other than 3'3'-CDNs remains incomplete. In this work, molecular dynamics simulations were used to provide an atomistic picture of the binding of 2'3'-cGAMP and one 3'3'-CDN (c-di-GMP) to hSTING. The results suggest that hSTING binds more strongly to 2'3'-cGAMP than to c-di-GMP, which prefers to bind with a more open and flexible state of hSTING. Finally, a potential "dock-lock-anchor" mechanism is proposed for the activation of hSTING upon the binding of a potent ligand. It is believed that deep insights into understanding the binding of hSTING with 3'3'-CDNs and the endogenous 2'3'-cGAMP would help to establish the principles underlying powerful 2'3'-cGAMP signaling and the nature of hSTING activation, as well as related drug design.
- Subjects :
- Protein Conformation
Molecular Dynamics Simulation
010402 general chemistry
Ligands
01 natural sciences
Biochemistry
Humans
Molecular Biology
Cyclic GMP
Principal Component Analysis
Binding Sites
010405 organic chemistry
Activator (genetics)
Chemistry
Organic Chemistry
Membrane Proteins
Ligand (biochemistry)
Guanine Nucleotides
0104 chemical sciences
Cell biology
Stimulator of interferon genes
Second messenger system
Mutation
Molecular Medicine
Cyclic dinucleotides
Protein Binding
Subjects
Details
- ISSN :
- 14397633
- Volume :
- 20
- Issue :
- 14
- Database :
- OpenAIRE
- Journal :
- Chembiochem : a European journal of chemical biology
- Accession number :
- edsair.doi.dedup.....fee5fc65a871d75ac3e05252e88b7ee0