4MKP

Crystal structure of human cGAS apo form

4MKP の概要

• エントリーDOI: 10.2210/pdb4mkp/pdb
• 分子名称: Cyclic GMP-AMP synthase, ZINC ION (3 entities in total)
• 機能のキーワード: nucleotidyltransferase, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytosol: Q8N884
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42614.45

構造登録者

Kato, K.,Ishii, R.,Ishitani, R.,Nureki, O. (登録日: 2013-09-05, 公開日: 2013-10-30, 最終更新日: 2023-11-08)

主引用文献

Kato, K.,Ishii, R.,Goto, E.,Ishitani, R.,Tokunaga, F.,Nureki, O.
Structural and Functional Analyses of DNA-Sensing and Immune Activation by Human cGAS
Plos One, 8:e76983-e76983, 2013

PubMed 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-κB and IRF3 pathways. Our results indicated that cGAS is a DNA sensor that efficiently activates the host immune system by inducing two distinct pathways.

PubMed: 24116191
DOI: 10.1371/journal.pone.0076983

実験手法

X-RAY DIFFRACTION (1.953 Å)