Human cGAS catalytic domain has an additional DNA-binding interface that enhances enzymatic activity and liquid-phase condensation.

ABSTRACT: The cyclic GMP-AMP synthase (cGAS)-cGAMP-STING pathway plays a key role in innate immunity, with cGAS sensing both pathogenic and mislocalized DNA in the cytoplasm. Human cGAS (h-cGAS) constitutes an important drug target for control of antiinflammatory responses that can contribute to the onset of autoimmune diseases. Recent studies have established that the positively charged N-terminal segment of cGAS contributes to enhancement of cGAS enzymatic activity as a result of DNA-induced liquid-phase condensation. We have identified an additional cGAS^CD-DNA interface (labeled site-C; CD, catalytic domain) in the crystal structure of a human SRY.cGAS^CD-DNA complex, with mutations along this basic site-C cGAS interface disrupting liquid-phase condensation, as monitored by c

SUBMITTER: Xie W 

PROVIDER: S-EPMC6575157 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature