4K98

Structure of Ternary Complex of cGAS with dsDNA and Bound 5 -pppG(2 ,5 )pG

4K98 の概要

• エントリーDOI: 10.2210/pdb4k98/pdb
• 関連するPDBエントリー: 4K8V 4K96 4K97 4K99 4K9A 4K9B
• 分子名称: Cyclic GMP-AMP synthase, DNA-F, DNA-R, ... (8 entities in total)
• 機能のキーワード: nucleotidyltransferase fold, transferase-dna complex, transferase/dna
• 由来する生物種: Mus musculus (mouse); 詳細
• 細胞内の位置: Cytoplasm, cytosol: Q8C6L5
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 53925.33

構造登録者

Gao, P.,Wu, Y.,Patel, D.J. (登録日: 2013-04-19, 公開日: 2013-05-15, 最終更新日: 2024-10-16)

主引用文献

Gao, P.,Ascano, M.,Wu, Y.,Barchet, W.,Gaffney, B.L.,Zillinger, T.,Serganov, A.A.,Liu, Y.,Jones, R.A.,Hartmann, G.,Tuschl, T.,Patel, D.J.
Cyclic [G(2',5')pA(3',5')p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase.
Cell(Cambridge,Mass.), 153:1094-1107, 2013

PubMed Abstract: Recent studies identified cyclic GMP-AMP (cGAMP) as a metazoan second messenger triggering an interferon response. cGAMP is generated from GTP and ATP by cytoplasmic dsDNA sensor cGAMP synthase (cGAS). We combined structural, chemical, biochemical, and cellular assays to demonstrate that this second messenger contains G(2',5')pA and A(3',5')pG phosphodiester linkages, designated c[G(2',5')pA(3',5')p]. We show that, upon dsDNA binding, cGAS is activated through conformational transitions, resulting in formation of a catalytically competent and accessible nucleotide-binding pocket for generation of c[G(2',5')pA(3',5')p]. We demonstrate that cyclization occurs in a stepwise manner through initial generation of 5'-pppG(2',5')pA prior to cyclization to c[G(2',5')pA(3',5')p], with the latter positioned precisely in the catalytic pocket. Mutants of cGAS dsDNA-binding or catalytic pocket residues exhibit reduced or abrogated activity. Our studies have identified c[G(2',5')pA(3',5')p] as a founding member of a family of metazoan 2',5'-containing cyclic heterodinucleotide second messengers distinct from bacterial 3',5' cyclic dinucleotides.

PubMed: 23647843
DOI: 10.1016/j.cell.2013.04.046

実験手法

X-RAY DIFFRACTION (1.94 Å)