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- EMDB-22408: 1:1 cGAS-nucleosome complex -

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Basic information

Entry
Database: EMDB / ID: EMD-22408
Title1:1 cGAS-nucleosome complex
Map data
Sample1:1 cGAS-nucleosome complex:
Histone H3.2 / Histone H4 / Histone H2A type 1 / Histone H2B type 1-C/E/F/G/I / (nucleic-acidNucleic acid) x 2 / Cyclic GMP-AMP synthase / ligand
Function / homology
Function and homology information


cyclic GMP-AMP synthase / positive regulation of cGMP-mediated signaling / cyclic-GMP-AMP synthase activity / regulation of immunoglobulin production / paracrine signaling / regulation of type I interferon production / negative regulation of double-strand break repair via homologous recombination / regulation of T cell activation / positive regulation of cAMP-mediated signaling / cellular response to exogenous dsRNA ...cyclic GMP-AMP synthase / positive regulation of cGMP-mediated signaling / cyclic-GMP-AMP synthase activity / regulation of immunoglobulin production / paracrine signaling / regulation of type I interferon production / negative regulation of double-strand break repair via homologous recombination / regulation of T cell activation / positive regulation of cAMP-mediated signaling / cellular response to exogenous dsRNA / negative regulation of megakaryocyte differentiation / positive regulation of defense response to virus by host / CENP-A containing nucleosome assembly / activation of innate immune response / DNA replication-independent nucleosome assembly / telomere capping / interleukin-7-mediated signaling pathway / chromatin silencing / determination of adult lifespan / positive regulation of type I interferon production / telomere organization / DNA replication-dependent nucleosome assembly / innate immune response in mucosa / nuclear nucleosome / rDNA heterochromatin assembly / negative regulation of gene expression, epigenetic / regulation of gene silencing by miRNA / nuclear chromosome / DNA-templated transcription, initiation / regulation of megakaryocyte differentiation / phosphatidylinositol-4,5-bisphosphate binding / nucleosome assembly / nucleosome / site of double-strand break / positive regulation of cellular senescence / double-strand break repair via nonhomologous end joining / defense response to virus / double-stranded DNA binding / chromatin organization / regulation of immune response / nuclear chromosome, telomeric region / antibacterial humoral response / antimicrobial humoral immune response mediated by antimicrobial peptide / blood coagulation / protein ubiquitination / protein heterodimerization activity / defense response to Gram-positive bacterium / nuclear chromatin / DNA repair / protein domain specific binding / GTP binding / cellular response to DNA damage stimulus / chromatin binding / cellular protein metabolic process / innate immune response / host cell nucleus / enzyme binding / protein-containing complex / RNA binding / DNA binding / extracellular space / extracellular exosome / membrane / extracellular region / nucleoplasm / ATP binding / identical protein binding / plasma membrane / metal ion binding / nucleus / cytosol
Histone H2B / TATA box binding protein associated factor (TAF) / CENP-T/Histone H4, histone fold / Histone H2A conserved site / Histone H2A, C-terminal domain / Mab-21 domain / Histone H4, conserved site / Histone H3/CENP-A / Histone-fold / Histone H4 ...Histone H2B / TATA box binding protein associated factor (TAF) / CENP-T/Histone H4, histone fold / Histone H2A conserved site / Histone H2A, C-terminal domain / Mab-21 domain / Histone H4, conserved site / Histone H3/CENP-A / Histone-fold / Histone H4 / Histone H2A / Histone H2A/H2B/H3
Histone H2A type 1 / Histone H4 / Histone H2B type 1-C/E/F/G/I / Histone H3.2 / Cyclic GMP-AMP synthase
Biological speciesHomo sapiens (human) / synthetic construct (others) / Mus musculus (house mouse)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsBoyer JA / Spangler CJ / Strauss JD / Cesmat AP / Liu P / McGinty RK / Zhang Q
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)1R35GM133498 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)R21CA234979 United States
CitationJournal: Science / Year: 2020
Title: Structural basis of nucleosome-dependent cGAS inhibition.
Authors: Joshua A Boyer / Cathy J Spangler / Joshua D Strauss / Andrew P Cesmat / Pengda Liu / Robert K McGinty / Qi Zhang /
Abstract: Cyclic GMP-AMP synthase (cGAS) recognizes cytosolic foreign or damaged DNA to activate the innate immune response to infection, inflammatory diseases, and cancer. In contrast, cGAS reactivity against ...Cyclic GMP-AMP synthase (cGAS) recognizes cytosolic foreign or damaged DNA to activate the innate immune response to infection, inflammatory diseases, and cancer. In contrast, cGAS reactivity against self-DNA in the nucleus is suppressed by chromatin tethering. We report a 3.3-angstrom-resolution cryo-electron microscopy structure of cGAS in complex with the nucleosome core particle. The structure reveals that cGAS employs two conserved arginines to anchor to the nucleosome acidic patch. The nucleosome binding interface exclusively occupies the strong dsDNA binding surface on cGAS and sterically prevents cGAS from oligomerizing into the functionally active 2:2 cGAS-dsDNA state. These findings provide a structural basis for how cGAS maintains an inhibited state in the nucleus and further exemplify the role of the nucleosome in regulating diverse nuclear protein functions.
Validation ReportPDB-ID: 7jo9

SummaryFull reportAbout validation report
History
DepositionAug 6, 2020-
Header (metadata) releaseSep 16, 2020-
Map releaseSep 16, 2020-
UpdateSep 23, 2020-
Current statusSep 23, 2020Processing site: RCSB / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.02
  • Imaged by UCSF Chimera
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  • Surface view colored by radius
  • Surface level: 0.02
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-7jo9
  • Surface level: 0.018
  • Imaged by UCSF Chimera
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

Downloads & links

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Map

FileDownload / File: emd_22408.map.gz / Format: CCP4 / Size: 137.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.91 Å/pix.
x 330 pix.
= 300.3 Å
0.91 Å/pix.
x 330 pix.
= 300.3 Å
0.91 Å/pix.
x 330 pix.
= 300.3 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.91 Å
Density
Contour LevelBy AUTHOR: 0.02 / Movie #1: 0.02
Minimum - Maximum-0.06437187 - 0.12129947
Average (Standard dev.)0.00016497131 (±0.0026456509)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions330330330
Spacing330330330
CellA=B=C: 300.30002 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z0.910.910.91
M x/y/z330330330
origin x/y/z0.0000.0000.000
length x/y/z300.300300.300300.300
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS330330330
D min/max/mean-0.0640.1210.000

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Supplemental data

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Sample components

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Entire 1:1 cGAS-nucleosome complex

EntireName: 1:1 cGAS-nucleosome complex / Details: mouse cGAS bound to the nucleosome in a 1:1 ratio / Number of components: 9

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Component #1: protein, 1:1 cGAS-nucleosome complex

ProteinName: 1:1 cGAS-nucleosome complex / Details: mouse cGAS bound to the nucleosome in a 1:1 ratio / Recombinant expression: No
MassTheoretical: 250 kDa
SourceSpecies: Homo sapiens (human)

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Component #2: protein, Histone H3.2

ProteinName: Histone H3.2 / Number of Copies: 2 / Recombinant expression: No
MassTheoretical: 15.421101 kDa
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Escherichia coli BL21(DE3) (bacteria)

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Component #3: protein, Histone H4

ProteinName: Histone H4 / Number of Copies: 2 / Recombinant expression: No
MassTheoretical: 11.394426 kDa
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Escherichia coli BL21(DE3) (bacteria)

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Component #4: protein, Histone H2A type 1

ProteinName: Histone H2A type 1 / Number of Copies: 2 / Recombinant expression: No
MassTheoretical: 13.990342 kDa
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Escherichia coli BL21(DE3) (bacteria)

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Component #5: protein, Histone H2B type 1-C/E/F/G/I

ProteinName: Histone H2B type 1-C/E/F/G/I / Number of Copies: 2 / Recombinant expression: No
MassTheoretical: 13.806018 kDa
SourceSpecies: Homo sapiens (human)
Source (engineered)Expression System: Escherichia coli BL21(DE3) (bacteria)

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Component #6: nucleic-acid, DNA (145-MER)

nucleic acidName: DNA (145-MER) / Class: DNA / Structure: OTHER / Synthetic: No
Sequence: (DA)(DT)(DC)(DG)(DG)(DA)(DT)(DG)(DT)(DA) (DT)(DA)(DT)(DA)(DT)(DC)(DT)(DG)(DA)(DC) (DA)(DC)(DG)(DT)(DG)(DC)(DC)(DT)(DG)(DG) (DA)(DG)(DA)(DC)(DT)(DA)(DG)(DG)(DG)(DA) (DG)(DT)(DA)(DA)(DT)(DC) ...Sequence:
(DA)(DT)(DC)(DG)(DG)(DA)(DT)(DG)(DT)(DA) (DT)(DA)(DT)(DA)(DT)(DC)(DT)(DG)(DA)(DC) (DA)(DC)(DG)(DT)(DG)(DC)(DC)(DT)(DG)(DG) (DA)(DG)(DA)(DC)(DT)(DA)(DG)(DG)(DG)(DA) (DG)(DT)(DA)(DA)(DT)(DC)(DC)(DC)(DC)(DT) (DT)(DG)(DG)(DC)(DG)(DG)(DT)(DT)(DA)(DA) (DA)(DA)(DC)(DG)(DC)(DG)(DG)(DG)(DG)(DG) (DA)(DC)(DA)(DG)(DC)(DG)(DC)(DG)(DT)(DA) (DC)(DG)(DT)(DG)(DC)(DG)(DT)(DT)(DT)(DA) (DA)(DG)(DC)(DG)(DG)(DT)(DG)(DC)(DT)(DA) (DG)(DA)(DG)(DC)(DT)(DG)(DT)(DC)(DT)(DA) (DC)(DG)(DA)(DC)(DC)(DA)(DA)(DT)(DT)(DG) (DA)(DG)(DC)(DG)(DG)(DC)(DC)(DT)(DC)(DG) (DG)(DC)(DA)(DC)(DC)(DG)(DG)(DG)(DA)(DT) (DT)(DC)(DT)(DC)(DG)(DA)(DT)
MassTheoretical: 45.610043 kDa
SourceSpecies: synthetic construct (others)

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Component #7: nucleic-acid, DNA (145-MER)

nucleic acidName: DNA (145-MER) / Class: DNA / Structure: OTHER / Synthetic: No
Sequence: (DA)(DT)(DC)(DG)(DA)(DG)(DA)(DA)(DT)(DC) (DC)(DC)(DG)(DG)(DT)(DG)(DC)(DC)(DG)(DA) (DG)(DG)(DC)(DC)(DG)(DC)(DT)(DC)(DA)(DA) (DT)(DT)(DG)(DG)(DT)(DC)(DG)(DT)(DA)(DG) (DA)(DC)(DA)(DG)(DC)(DT) ...Sequence:
(DA)(DT)(DC)(DG)(DA)(DG)(DA)(DA)(DT)(DC) (DC)(DC)(DG)(DG)(DT)(DG)(DC)(DC)(DG)(DA) (DG)(DG)(DC)(DC)(DG)(DC)(DT)(DC)(DA)(DA) (DT)(DT)(DG)(DG)(DT)(DC)(DG)(DT)(DA)(DG) (DA)(DC)(DA)(DG)(DC)(DT)(DC)(DT)(DA)(DG) (DC)(DA)(DC)(DC)(DG)(DC)(DT)(DT)(DA)(DA) (DA)(DC)(DG)(DC)(DA)(DC)(DG)(DT)(DA)(DC) (DG)(DC)(DG)(DC)(DT)(DG)(DT)(DC)(DC)(DC) (DC)(DC)(DG)(DC)(DG)(DT)(DT)(DT)(DT)(DA) (DA)(DC)(DC)(DG)(DC)(DC)(DA)(DA)(DG)(DG) (DG)(DG)(DA)(DT)(DT)(DA)(DC)(DT)(DC)(DC) (DC)(DT)(DA)(DG)(DT)(DC)(DT)(DC)(DC)(DA) (DG)(DG)(DC)(DA)(DC)(DG)(DT)(DG)(DT)(DC) (DA)(DG)(DA)(DT)(DA)(DT)(DA)(DT)(DA)(DC) (DA)(DT)(DC)(DC)(DG)(DA)(DT)
MassTheoretical: 45.13877 kDa
SourceSpecies: synthetic construct (others)

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Component #8: protein, Cyclic GMP-AMP synthase

ProteinName: Cyclic GMP-AMP synthase / Number of Copies: 1 / Recombinant expression: No
MassTheoretical: 42.984664 kDa
SourceSpecies: Mus musculus (house mouse)
Source (engineered)Expression System: Escherichia coli BL21(DE3) (bacteria)

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Component #9: ligand, ZINC ION

LigandName: ZINC ION / Number of Copies: 1 / Recombinant expression: No
MassTheoretical: 6.540905 MDa

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Experimental details

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Sample preparation

SpecimenSpecimen state: Particle / Method: cryo EM
Sample solutionSpecimen conc.: 1 mg/mL / pH: 7.5
Support filmInstrument: Pelco easiGlow
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Temperature: 293 K / Humidity: 95 %

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Electron microscopy imaging

Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company
ImagingMicroscope: FEI TALOS ARCTICA
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Electron dose: 53 e/Å2 / Illumination mode: FLOOD BEAM
LensImaging mode: BRIGHT FIELD
Specimen HolderModel: OTHER
CameraDetector: OTHER

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Image acquisition

Image acquisitionNumber of digital images: 2100

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Image processing

ProcessingMethod: single particle reconstruction / Number of projections: 116377
3D reconstructionSoftware: RELION / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF
FSC plot (resolution estimation)

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Atomic model buiding

Modeling #1Refinement space: REAL
Input PDB model: 6FQ5, 4K8V
Output model

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