Mechanisms of phase-separation-mediated cGAS activation revealed by dcFCCS.

ABSTRACT: Cyclic GMP-AMP synthase (cGAS), as a DNA sensor, plays an important role in cGAS-STING pathway, which further induces expression of type I interferon as the innate immune response. Previous studies reported that liquid-liquid phase separation (LLPS) driven by cGAS and long DNA is essential to promote catalytic activity of cGAS to produce a second messenger, cyclic GMP-AMP (cGAMP). However, the molecular mechanism of LLPS promoting cGAS activity is still unclear. Here, we applied dual-color fluorescence cross-correlation spectroscopy (dcFCCS), a highly sensitive and quantitative method, to characterize phase separation driven by cGAS and DNA from miscible individual molecule to micronscale. Thus, we captured nanoscale condensates formed by cGAS at close-to-physiological concentration and qu

SUBMITTER: Yao Y 

PROVIDER: S-EPMC9896928 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature