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Human STING is a proton channel.

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.

SUBMITTER: Liu B

PROVIDER: S-EPMC11260435 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Human STING is a proton channel.

Liu Bingxu B Carlson Rebecca J RJ Pires Ivan S IS Gentili Matteo M Feng Ellie E Hellier Quentin Q Schwartz Marc A MA Blainey Paul C PC Irvine Darrell J DJ Hacohen Nir N

Science (New York, N.Y.) 20230803 6657

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 ...[more]

PMID: 37535724

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