4KM5

X-ray crystal structure of human cyclic GMP-AMP synthase (cGAS)

4KM5 の概要

• エントリーDOI: 10.2210/pdb4km5/pdb
• 分子名称: Cyclic GMP-AMP synthase, ZINC ION (3 entities in total)
• 機能のキーワード: dna sensor, innate immunity, zinc finger, nucleotidyl transferase, dna, cytoplasmic, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytosol . Note=(Microbial infection) Upon infection with virulent M: Q8N884
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 43055.88

構造登録者

Kranzusch, P.J.,Lee, A.S.Y.,Berger, J.M.,Doudna, J.A. (登録日: 2013-05-08, 公開日: 2013-05-29, 最終更新日: 2024-02-28)

主引用文献

Kranzusch, P.J.,Lee, A.S.,Berger, J.M.,Doudna, J.A.
Structure of Human cGAS Reveals a Conserved Family of Second-Messenger Enzymes in Innate Immunity.
Cell Rep, 3:1362-1368, 2013

PubMed Abstract: Innate immune recognition of foreign nucleic acids induces protective interferon responses. Detection of cytosolic DNA triggers downstream immune signaling through activation of cyclic GMP-AMP synthase (cGAS). We report here the crystal structure of human cGAS, revealing an unanticipated zinc-ribbon DNA-binding domain appended to a core enzymatic nucleotidyltransferase scaffold. The catalytic core of cGAS is structurally homologous to the RNA-sensing enzyme, 2'-5' oligo-adenylate synthase (OAS), and divergent C-terminal domains account for specific ligand-activation requirements of each enzyme. We show that the cGAS zinc ribbon is essential for STING-dependent induction of the interferon response and that conserved amino acids displayed within the intervening loops are required for efficient cytosolic DNA recognition. These results demonstrate that cGAS and OAS define a family of innate immunity sensors and that structural divergence from a core nucleotidyltransferase enables second-messenger responses to distinct foreign nucleic acids.

PubMed: 23707061
DOI: 10.1016/j.celrep.2013.05.008

実験手法

X-RAY DIFFRACTION (2.499 Å)