Human STING is a proton channel
Broad Institute · Allen Institute · +7 more institutions
Abstract
Proton leakage from organelles is a common signal for noncanonical light chain 3B (LC3B) lipidation and inflammasome activation, processes induced upon stimulator of interferon genes (STING) activation. On the basis of structural analysis, we hypothesized that human STING is a proton channel. Indeed, we found that STING activation induced a pH increase in the Golgi and that STING reconstituted in liposomes enabled transmembrane proton transport. Compound 53 (C53), a STING agonist that binds the putative channel interface, blocked STING-induced proton flux in the Golgi and in liposomes. STING-induced LC3B lipidation and inflammasome activation were also inhibited by C53, suggesting that STING's channel activity…
Citation impact
- FWCI
- 28.98
- Percentile
- 100%
- References
- 36
Authors
10- BLBingxu LiuCorresponding
Broad Institute, Allen Institute, Koch Institute for Integrative Cancer Research At MIT, Massachusetts Institute of Technology
- RJRebecca J. CarlsonCorresponding
Broad Institute, Massachusetts Institute of Technology
- ISIvan S. PiresCorresponding
Allen Institute, Koch Institute for Integrative Cancer Research At MIT
- MGMatteo GentiliCorresponding
Broad Institute
- EFEllie Feng
Broad Institute, Massachusetts Institute of Technology
Topics & keywords
- Sting
- Stimulator of interferon genes
- Inflammasome
- Chemistry
- Cell biology
- Transmembrane protein
- Golgi apparatus
- Lipid-anchored protein