4KB6

Structure of porcine cyclic GMP AMP synthase (CGAS) in complex with DNA, ATP and GTP

4KB6 の概要

• エントリーDOI: 10.2210/pdb4kb6/pdb
• 関連するPDBエントリー: 4JLX 4JLZ
• 分子名称: Uncharacterized protein, DNA (5'-D(P*CP*GP*AP*CP*GP*CP*TP*AP*GP*CP*GP*TP*CP*G)-3'), ZINC ION, ... (7 entities in total)
• 機能のキーワード: oas-like fold, receptor, immunity, cgas, double stranded dna, gtp, cytosol, transferase-dna complex, transferase/dna
• 由来する生物種: Sus scrofa (pigs,swine,wild boar); 詳細
• 細胞内の位置: Cytoplasm, cytosol : I3LM39
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 52153.82

構造登録者

Deimling, T.,Hopfner, K.-P. (登録日: 2013-04-23, 公開日: 2013-06-05, 最終更新日: 2023-09-20)

主引用文献

Civril, F.,Deimling, T.,de Oliveira Mann, C.C.,Ablasser, A.,Moldt, M.,Witte, G.,Hornung, V.,Hopfner, K.P.
Structural mechanism of cytosolic DNA sensing by cGAS.
Nature, 498:332-337, 2013

PubMed Abstract: Cytosolic DNA arising from intracellular bacterial or viral infections is a powerful pathogen-associated molecular pattern (PAMP) that leads to innate immune host defence by the production of type I interferon and inflammatory cytokines. Recognition of cytosolic DNA by the recently discovered cyclic-GMP-AMP (cGAMP) synthase (cGAS) induces the production of cGAMP to activate the stimulator of interferon genes (STING). Here we report the crystal structure of cGAS alone and in complex with DNA, ATP and GTP along with functional studies. Our results explain the broad DNA sensing specificity of cGAS, show how cGAS catalyses dinucleotide formation and indicate activation by a DNA-induced structural switch. cGAS possesses a remarkable structural similarity to the antiviral cytosolic double-stranded RNA sensor 2'-5'oligoadenylate synthase (OAS1), but contains a unique zinc thumb that recognizes B-form double-stranded DNA. Our results mechanistically unify dsRNA and dsDNA innate immune sensing by OAS1 and cGAS nucleotidyl transferases.

PubMed: 23722159
DOI: 10.1038/nature12305

実験手法

X-RAY DIFFRACTION (3.0754 Å)