Human STING is a proton channel-Reference-Cited by-同舟云学术

Human STING is a proton channel

Published:2023-08-04 Issue:6657 Volume:381 Page:508-514
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Liu Bingxu¹²³^ORCID,Carlson Rebecca J.¹⁴^ORCID,Pires Ivan S.³^ORCID,Gentili Matteo¹^ORCID,Feng Ellie¹⁵,Hellier Quentin¹^ORCID,Schwartz Marc A.¹⁶⁷⁸^ORCID,Blainey Paul C.¹³⁵^ORCID,Irvine Darrell J.³^ORCID,Hacohen Nir¹⁹^ORCID

Affiliation:

1. Broad Institute, Cambridge, MA, USA.

2. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.

3. The Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA, USA.

4. Massachusetts Institute of Technology, Department of Health Sciences and Technology, Cambridge, MA, USA.

5. Massachusetts Institute of Technology, Department of Biological Engineering, Cambridge, MA, USA.

6. Department of Pediatrics, Harvard Medical School, Boston, MA, USA.

7. Division of Hematology and Oncology, Boston Children’s Hospital, Boston, MA, USA.

8. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

9. Massachusetts General Hospital Cancer Center, Boston, MA, USA.

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 is critical for these two processes. Thus, STING’s interferon-induction function can be decoupled from its roles in LC3B lipidation and inflammasome activation.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/science.adf8974

Reference34 articles.

1. STING is a direct innate immune sensor of cyclic di-GMP

2. Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway

3. Cyclic GMP-AMP Is an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA

4. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling

5. Autophagy induction via STING trafficking is a primordial function of the cGAS pathway

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