美国博德研究所
研究人员表示，质子从细胞器中泄漏是非经典轻链3B（LC3B）脂化和炎性小体激活的共同信号，这些过程会在干扰素基因刺激因子（STING）激活时诱发。
根据结构分析，研究人员假设人类STING是一个质子通道。事实上，研究人员发现STING激活会诱导高尔基体中pH值的升高，而在脂质体中重组的STING能够实现跨膜质子转运。化合物53（C53）是一种STING激动剂，能结合推测的通道接口，它能阻断STING在高尔基体和脂质体中诱导的质子流量。C53还抑制了STING诱导的LC3B脂化和炎性小体激活，这表明STING的通道活性对这两个过程至关重要。因此，STING的干扰素诱导功能可以与其在LC3B脂化和炎性小体活化中的作用相分离。
附：英文原文
Title: Human STING is a proton channel
Author: Bingxu Liu, Rebecca J. Carlson, Ivan S. Pires, Matteo Gentili, Ellie Feng, Quentin Hellier, Marc A. Schwartz, Paul C. Blainey, Darrell J. Irvine, Nir Hacohen
Issue&Volume: 2023-08-04
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.
DOI: adf8974
Source: https://www.science.org/doi/full/10.1126/science.adf8974