Dataset Information

Structural and functional analyses of DNA-sensing and immune activation by human cGAS.

ABSTRACT: The detection of cytosolic DNA, derived from pathogens or host cells, by cytosolic receptors is essential for appropriate host immune responses. Cyclic GMP-AMP synthase (cGAS) is a newly identified cytosolic DNA receptor that produces cyclic GMP-AMP, which activates stimulator of interferon genes (STING), resulting in TBK1-IRF3 pathway activation followed by the production of type I interferons. Here we report the crystal structure of human cGAS. The structure revealed that a cluster of lysine and arginine residues forms the positively charged DNA binding surface of human cGAS, which is important for the STING-dependent immune activation. A structural comparison with other previously determined cGASs and our functional analyses suggested that a conserved zinc finger motif and a leucine residue on the DNA binding surface are crucial for the DNA-specific immune response of human cGAS, consistent with previous work. These structural features properly orient the DNA binding to cGAS, which is critical for DNA-induced cGAS activation and STING-dependent immune activation. Furthermore, we showed that the cGAS-induced activation of STING also involves the activation of the NF-?B and IRF3 pathways. Our results indicated that cGAS is a DNA sensor that efficiently activates the host immune system by inducing two distinct pathways.

SUBMITTER: Kato K

PROVIDER: S-EPMC3792152 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Structural and functional analyses of DNA-sensing and immune activation by human cGAS.

Kato Kazuki K Ishii Ryohei R Goto Eiji E Ishitani Ryuichiro R Tokunaga Fuminori F Nureki Osamu O

PloS one 20131007 10

The detection of cytosolic DNA, derived from pathogens or host cells, by cytosolic receptors is essential for appropriate host immune responses. Cyclic GMP-AMP synthase (cGAS) is a newly identified cytosolic DNA receptor that produces cyclic GMP-AMP, which activates stimulator of interferon genes (STING), resulting in TBK1-IRF3 pathway activation followed by the production of type I interferons. Here we report the crystal structure of human cGAS. The structure revealed that a cluster of lysine a ...[more]

PMID: 24116191

Similar Datasets

Project description:Background and aimsCyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) (cGAMP) synthase (cGAS) and stimulator of interferon genes (STING) are key components of the innate immune system. This study aims to evaluate the research of cGAS-STING pathway and predict the hotspots and developing trends in this field using bibliometric analysis.MethodsWe retrieved publications from Science Citation Index Expanded (SCI-expanded) of Web of Science Core Collection (WoSCC) in 1975-2021 on 16 March 2022. We examined the retrieved data by bibliometrix package in R software, VOSviewer and CiteSpace were used for visualizing the trends and hotspots of research on the cGAS-STING pathway.ResultsWe identified 1047 original articles and reviews on the cGAS-STING pathway published between 1975 and 2021. Before 2016, the publication trend was increasing steadily, but there was a significant increase after 2016. The United States of America (USA) produced the highest number of papers (Np) and took the highest number of citations (Nc), followed by China and Germany. The University of Texas System and Frontiers in Immunology were the most prolific affiliation and journal respectively. In addition, collaboration network analysis showed that there were tight collaborations among the USA, China and some European countries, so the top 10 affiliations were all from these countries and regions. The paper published by Sun LJ in 2013 reached the highest local citation score (LCS). Keywords co-occurrence and co-citation cluster analysis revealed that inflammation, senescence, and tumor were popular terms related to the cGAS-STING pathway recently. Keywords burst detection suggested that STING-dependent innate immunity and NF-κB-dependent broad antiviral response were newly-emerged hotspots in this area.ConclusionsThis bibliometric analysis shows that publications related to the cGAS-STING pathway tend to increase continuously. The research focus has shifted from the mechanism how cGAS senses dsDNA and cGAMP binds to STING to the roles of the cGAS-STING pathway in different pathological state.

Dataset Information

Structural and functional analyses of DNA-sensing and immune activation by human cGAS.

Publications

Structural and functional analyses of DNA-sensing and immune activation by human cGAS.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets