SASDEQ9: Cyclic GMP-AMP synthase (cGAS) with cyclic guanosine monophosphat...

基本情報

• 登録情報: データベース: SASBDB / ID: SASDEQ9

試料

Cyclic GMP-AMP synthase (cGAS) with cyclic guanosine monophosphate–adenosine monophosphate (2'3'-cGAMP)

• Cyclic GMP-AMP synthase (protein), cGASChildren's Global Assessment Scale, Homo sapiens
• 2'-O,5'-O-((adenosine-3'-O,5'-O-diyl)bisphosphinico)guanosine (other), 2′3′-cGAMP

機能・相同性

分子機能:

cyclic GMP-AMP synthase / 2',3'-cyclic GMP-AMP synthase activity / STING mediated induction of host immune responses / 傍分泌 / poly-ADP-D-ribose modification-dependent protein binding / cGAS/STING signaling pathway / regulation of immunoglobulin production / regulation of T cell activation / pattern recognition receptor signaling pathway / negative regulation of cGAS/STING signaling pathway / cytoplasmic pattern recognition receptor signaling pathway / cellular response to exogenous dsRNA / cGMP-mediated signaling / positive regulation of type I interferon production / negative regulation of double-strand break repair via homologous recombination / nucleosome binding / positive regulation of defense response to virus by host / phosphatidylinositol-4,5-bisphosphate binding / activation of innate immune response / cAMP-mediated signaling / molecular condensate scaffold activity / determination of adult lifespan / positive regulation of cellular senescence / site of double-strand break / double-stranded DNA binding / defense response to virus / nuclear body / DNA修復 / 自然免疫系 / DNA damage response / chromatin binding / GTP binding / protein homodimerization activity / DNA binding / 核質 / ATP binding / metal ion binding / 細胞核 / 細胞膜 / 細胞質基質 / 細胞質

ドメイン・相同性:

Mab-21-like, nucleotidyltransferase domain / Mab-21-like, HhH/H2TH-like domain / Mab-21 protein HhH/H2TH-like domain / Mab-21 protein nucleotidyltransferase domain / Mab-21-like / Mab-21

構成要素:

Cyclic GMP-AMP synthase

• 生物種: Homo sapiens (ヒト)
• 引用: ジャーナル: EMBO Rep / 年: 2019; タイトル: cGAS facilitates sensing of extracellular cyclic dinucleotides to activate innate immunity.; 著者: Haipeng Liu / Pedro Moura-Alves / Gang Pei / Hans-Joachim Mollenkopf / Robert Hurwitz / Xiangyang Wu / Fei Wang / Siyu Liu / Mingtong Ma / Yiyan Fei / Chenggang Zhu / Anne-Britta Koehler / Dagmar Oberbeck-Mueller / Karin Hahnke / Marion Klemm / Ute Guhlich-Bornhof / Baoxue Ge / Anne Tuukkanen / Michael Kolbe / Anca Dorhoi / Stefan He Kaufmann / ; 要旨: Cyclic dinucleotides (CDNs) are important second messenger molecules in prokaryotes and eukaryotes. Within host cells, cytosolic CDNs are detected by STING and alert the host by activating innate immunity characterized by type I interferon (IFN) responses. Extracellular bacteria and dying cells can release CDNs, but sensing of extracellular CDNs (eCDNs) by mammalian cells remains elusive. Here, we report that endocytosis facilitates internalization of eCDNs. The DNA sensor cGAS facilitates sensing of endocytosed CDNs, their perinuclear accumulation, and subsequent STING-dependent release of type I IFN Internalized CDNs bind cGAS directly, leading to its dimerization, and the formation of a cGAS/STING complex, which may activate downstream signaling. Thus, eCDNs comprise microbe- and danger-associated molecular patterns that contribute to host-microbe crosstalk during health and disease.

登録者

• Anne Tuukkanen (EMBL-Hamburg, European Molecular Biology Laboratory (EMBL) - Hamburg outstation, Notkestraße 85, Geb. 25A, 22607 Hamburg, Deutschland, Germany)

モデル

• モデル #2780: ; タイプ: mix / ダミー原子の半径: 1.90 A / カイ2乗値: 1.138 / P-value: 0.000013; Omokage検索でこの集合体の類似形状データを探す (詳細)
• モデル #2781: ; タイプ: mix / ダミー原子の半径: 1.90 A / カイ2乗値: 1.138 / P-value: 0.000013; Omokage検索でこの集合体の類似形状データを探す (詳細)
• モデル #2782: ; タイプ: mix / ダミー原子の半径: 1.90 A / カイ2乗値: 1.138 / P-value: 0.000013; Omokage検索でこの集合体の類似形状データを探す (詳細)
• モデル #2783: ; タイプ: mix / ダミー原子の半径: 1.90 A / カイ2乗値: 1.138 / P-value: 0.000013; Omokage検索でこの集合体の類似形状データを探す (詳細)

試料

• 試料: 名称: Cyclic GMP-AMP synthase (cGAS) with cyclic guanosine monophosphate–adenosine monophosphate (2'3'-cGAMP); 試料濃度: 9 mg/ml / Entity id: 1448 / 1449
• バッファ: 名称: 20 mM HEPES / pH: 7.4

要素 #1448

名称: cGASChildren's Global Assessment Scale / タイプ: protein / 記述: Cyclic GMP-AMP synthase / 分子量: 61.419 / 分子数: 2 / 由来: Homo sapiens / 参照: UniProt: Q8N884
配列:

MQPWHGKAMQ RASEAGATAP KASARNARGA PMDPTESPAA PEAALPKAGK FGPARKSGSR QKKSAPDTQE RPPVRATGAR AKKAPQRAQD TQPSDATSAP GAEGLEPPAA REPALSRAGS CRQRGARCST KPRPPPGPWD VPSPGLPVSA PILVRRDAAP GASKLRAVLE KLKLSRDDIS TAAGMVKGVV DHLLLRLKCD SAFRGVGLLN TGSYYEHVKI SAPNEFDVMF KLEVPRIQLE EYSNTRAYYF VKFKRNPKEN PLSQFLEGEI LSASKMLSKF RKIIKEEIND IKDTDVIMKR KRGGSPAVTL LISEKISVDI TLALESKSSW PASTQEGLRI QNWLSAKVRK QLRLKPFYLV PKHAKEGNGF QEETWRLSFS HIEKEILNNH GKSKTCCENK EEKCCRKDCL KLMKYLLEQL KERFKDKKHL DKFSSYHVKT AFFHVCTQNP QDSQWDRKDL GLCFDNCVTY FLQCLRTEKL ENYFIPEFNL FSSNLIDKRS KEFLTKQIEY ERNNEFPVFD EFLEYPYDVP DYAAAALEHH HHHH

要素 #1449

名称: 2′3′-cGAMP / タイプ: other
記述: 2'-O,5'-O-((adenosine-3'-O,5'-O-diyl)bisphosphinico)guanosine
分子量: 0.674 / 分子数: 2
配列:

C20H24N10O 13P2

実験情報

• ビーム: 設備名称: PETRA III EMBL P12 / 地域: Hamburg / 国: Germany / 線源: X-ray synchrotronシンクロトロン / 波長: 0.1241 Å / スペクトロメータ・検出器間距離: 3 mm
• 検出器: 名称: Pilatus 2M

スキャン

タイトル: Cyclic GMP-AMP synthase (cGAS) with cyclic guanosine monophosphate–adenosine monophosphate (2'3'-cGAMP)
測定日: 2017年4月25日 / 保管温度: 10 °C / セル温度: 20 °C / 照射時間: 1 sec. / フレーム数: 3600 / 単位: 1/nm /

	Min	Max
Q	0.1385	5.0254

距離分布関数 P(R)

ソフトウェア P(R): GNOM 5.0 / ポイント数: 674 /

	Min	Max
Q	0.179742	2.02844
P(R) point	1	674
R	0	14.11

結果

カーブのタイプ: sec /

	実験値	Porod
分子量	98 kDa	74.7 kDa
体積	-	127 nm3

	P(R)	P(R) error	Guinier	Guinier error
前方散乱 I0	2559	25.6	2543.39	10.14
慣性半径, Rg	4.118 nm	0.21	3.94 nm	0.9

	Min	Max	Error
D	-	14.11	0.71
Guinier point	16	70	-