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

Basic information

• Entry: Database: SASBDB / ID: SASDEQ9

Sample

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

Function / homology

Function:

cyclic GMP-AMP synthase / 2',3'-cyclic GMP-AMP synthase activity / STING mediated induction of host immune responses / paracrine signaling / 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 double-strand break repair via homologous recombination / negative regulation of cGAS/STING signaling pathway / cellular response to exogenous dsRNA / cytoplasmic pattern recognition receptor signaling pathway / cGMP-mediated signaling / cAMP-mediated signaling / nucleosome binding / positive regulation of type I interferon production / positive regulation of defense response to virus by host / phosphatidylinositol-4,5-bisphosphate binding / activation of innate immune response / 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 repair / innate immune response / DNA damage response / chromatin binding / GTP binding / protein homodimerization activity / DNA binding / nucleoplasm / ATP binding / metal ion binding / nucleus / plasma membrane / cytosol / cytoplasm

Domain/homology:

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

Component:

Cyclic GMP-AMP synthase

• Biological species: Homo sapiens (human)
• Citation: Journal: EMBO Rep / Year: 2019; Title: cGAS facilitates sensing of extracellular cyclic dinucleotides to activate innate immunity.; Authors: 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 / ; Abstract: 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.

Contact author

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

Models

• Model #2780: ; Type: mix / Radius of dummy atoms: 1.90 A / Chi-square value: 1.138 / P-value: 0.000013; Search similar-shape structures of this assembly by Omokage search (details)
• Model #2781: ; Type: mix / Radius of dummy atoms: 1.90 A / Chi-square value: 1.138 / P-value: 0.000013; Search similar-shape structures of this assembly by Omokage search (details)
• Model #2782: ; Type: mix / Radius of dummy atoms: 1.90 A / Chi-square value: 1.138 / P-value: 0.000013; Search similar-shape structures of this assembly by Omokage search (details)
• Model #2783: ; Type: mix / Radius of dummy atoms: 1.90 A / Chi-square value: 1.138 / P-value: 0.000013; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: Cyclic GMP-AMP synthase (cGAS) with cyclic guanosine monophosphate–adenosine monophosphate (2'3'-cGAMP); Specimen concentration: 9 mg/ml / Entity id: 1448 / 1449
• Buffer: Name: 20 mM HEPES / pH: 7.4

Entity #1448

Name: cGASChildren's Global Assessment Scale / Type: protein / Description: Cyclic GMP-AMP synthase / Formula weight: 61.419 / Num. of mol.: 2 / Source: Homo sapiens / References: UniProt: Q8N884
Sequence:

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

Entity #1449

Name: 2′3′-cGAMP / Type: other
Description: 2'-O,5'-O-((adenosine-3'-O,5'-O-diyl)bisphosphinico)guanosine
Formula weight: 0.674 / Num. of mol.: 2
Sequence:

C20H24N10O 13P2

Experimental information

• Beam: Instrument name: PETRA III EMBL P12 / City: Hamburg / 国: Germany / Type of source: X-ray synchrotronSynchrotron / Wavelength: 0.1241 Å / Dist. spec. to detc.: 3 mm
• Detector: Name: Pilatus 2M

Scan

Title: Cyclic GMP-AMP synthase (cGAS) with cyclic guanosine monophosphate–adenosine monophosphate (2'3'-cGAMP)
Measurement date: Apr 25, 2017 / Storage temperature: 10 °C / Cell temperature: 20 °C / Exposure time: 1 sec. / Number of frames: 3600 / Unit: 1/nm /

	Min	Max
Q	0.1385	5.0254

Distance distribution function P(R)

Sofotware P(R): GNOM 5.0 / Number of points: 674 /

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

Result

Type of curve: sec /

	Experimental	Porod
MW	98 kDa	74.7 kDa
Volume	-	127 nm3

	P(R)	P(R) error	Guinier	Guinier error
Forward scattering, I0	2559	25.6	2543.39	10.14
Radius of gyration, Rg	4.118 nm	0.21	3.94 nm	0.9

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