Human STING is a proton channel

• 成果类型: Article
• 署名作者: Liu, Bingxu; Carlson, Rebecca J.; Pires, Ivan S.; Gentili, Matteo; Feng, Ellie; Hellier, Quentin; Schwartz, Marc A.; Blainey, Paul C.; Irvine, Darrell J.; Hacohen, Nir
• 署名单位: Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT); Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9260
• DOI: 10.1126/science.adf8974
• 发表日期: 2023-08-04
• 页码: 508-514
• 关键词: cyclic gmp-amp; membrane-proteins; reconstitution; activate; sensor

摘要

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.