Structural basis of nucleosome-dependent cGAS inhibition

doi:10.1126/science.abd0609

GSTDTAP > 气候变化

DOI	10.1126/science.abd0609
	Structural basis of nucleosome-dependent cGAS inhibition
	Joshua A. Boyer; Cathy J. Spangler; Joshua D. Strauss; Andrew P. Cesmat; Pengda Liu; Robert K. McGinty; Qi Zhang
	2020-10-23
发表期刊	Science
出版年	2020
英文摘要	A fundamental mammalian defense mechanism against pathogens and damaged cellular DNA is to recognize DNA fragments in the cytosol and trigger an inflammatory response. The cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS) that recognizes cytosolic DNA is also found in the nucleus, but here its activity is suppressed by tethering to chromatin. Two papers now report cryo–electron microscopy structures of cGAS bound to the nucleosome core particle (NCP). Kujirai et al. observed a structure with two cGAS molecules bridging two NCPs, whereas Boyer et al. observed cGAS bound to a single nucleosome. Together, these structures show how cGAS is prevented from autoreactivity toward host DNA. Science , this issue p. [455][1], p. [450][2] Cyclic guanosine monophosphate (GMP)–adenosine monophosphate (AMP) synthase (cGAS) recognizes cytosolic foreign or damaged DNA to activate the innate immune response to infection, inflammatory diseases, and cancer. By contrast, cGAS reactivity against self-DNA in the nucleus is suppressed by chromatin tethering. We report a 3.3-angstrom-resolution cryo–electron microscopy structure of cGAS in complex with the nucleosome core particle. The structure reveals that cGAS uses two conserved arginines to anchor to the nucleosome acidic patch. The nucleosome-binding interface exclusively occupies the strong double-stranded DNA (dsDNA)–binding surface on cGAS and sterically prevents cGAS from oligomerizing into the functionally active 2:2 cGAS-dsDNA state. These findings provide a structural basis for how cGAS maintains an inhibited state in the nucleus and further exemplify the role of the nucleosome in regulating diverse nuclear protein functions. [1]: /lookup/doi/10.1126/science.abd0237 [2]: /lookup/doi/10.1126/science.abd0609
领域	气候变化 ; 资源环境
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/300295
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Joshua A. Boyer,Cathy J. Spangler,Joshua D. Strauss,et al. Structural basis of nucleosome-dependent cGAS inhibition[J]. Science,2020.
APA	Joshua A. Boyer.,Cathy J. Spangler.,Joshua D. Strauss.,Andrew P. Cesmat.,Pengda Liu.,...&Qi Zhang.(2020).Structural basis of nucleosome-dependent cGAS inhibition.Science.
MLA	Joshua A. Boyer,et al."Structural basis of nucleosome-dependent cGAS inhibition".Science (2020).