The Cytosolic DNA Sensor cGAS Forms an Oligomeric Complex with DNA and Undergoes Switch-like Conformational Changes in the Activation Loop.
Xu Zhang,Jiaxi Wu,Fenghe Du,Hui Xu,Lijun Sun,Zhe Chen,Chad A. Brautigam,Xuewu Zhang,Zhijian J. Chen +8 more
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TLDR
The crystal structures of human cGAS are reported in its apo form, representing its autoinhibited conformation as well as in its cGAMP- and sulfate-bound forms, revealing switch-like conformational changes of an activation loop that result in the rearrangement of the catalytic site.About:
This article is published in Cell Reports.The article was published on 2014-02-13 and is currently open access. It has received 308 citations till now. The article focuses on the topics: Cyclic GMP-AMP synthase.read more
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Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing
TL;DR: Recent advances in understanding of the cGAS–STING pathway are reviewed, focusing on the regulatory mechanisms and roles of this pathway in heath and disease.
Journal ArticleDOI
cGAS surveillance of micronuclei links genome instability to innate immunity
Karen J. Mackenzie,Paula Carroll,Carol Anne Martin,Olga Murina,Adeline Fluteau,Daniel J. Simpson,Nelly Olova,Hannah Sutcliffe,Jacqueline K. Rainger,Andrea Leitch,Ruby T. Osborn,Ann P. Wheeler,Marcin Nowotny,Nick Gilbert,Tamir Chandra,Martin A M Reijns,Andrew P. Jackson +16 more
TL;DR: It is reported that cGAS localizes to micronuclei arising from genome instability in a mouse model of monogenic autoinflammation, after exogenous DNA damage and spontaneously in human cancer cells, and it is established that interferon-stimulated gene expression is induced inmicronucleated cells, concluding that micronsuclei represent an important source of immunostimulatory DNA.
Journal ArticleDOI
Innate Immune Sensing and Signaling of Cytosolic Nucleic Acids
Jiaxi Wu,Zhijian J. Chen +1 more
TL;DR: Recent advances in understanding the mechanism of nucleic acid sensing and signaling in the cytosol of mammalian cells as well as the emerging role of cytosolic nucleic acids in autoimmunity are reviewed.
Journal ArticleDOI
Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology.
Eva Schrezenmeier,Thomas Dörner +1 more
TL;DR: Mechanistic data give insights into the immunomodulatory potency of hydroxychloroquine and provide the rationale to search for more potent and/or selective inhibitors in antimalarial drugs.
Journal ArticleDOI
The cGAS-cGAMP-STING Pathway of Cytosolic DNA Sensing and Signaling
TL;DR: This review focuses on the mechanism of DNA sensing by the newly discovered cGAS-cGAMP-STING pathway and highlights recent progress in dissecting the in vivo functions of this pathway in immune defense as well as autoimmunity.
References
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Zbyszek Otwinowski,Wladek Minor +1 more
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