[English] 日本語
Yorodumi
- PDB-7jo9: 1:1 cGAS-nucleosome complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7jo9
Title1:1 cGAS-nucleosome complex
Components
  • (DNA (145-MER)) x 2
  • Cyclic GMP-AMP synthase
  • Histone H2A type 1
  • Histone H2B type 1-C/E/F/G/I
  • Histone H3.2
  • Histone H4
KeywordsDNA Binding Protein/DNA/Transferase / cGAS / nucleosome / cyclic GMP-AMP synthase / DNA Binding Protein-DNA-Transferase complex
Function / homology
Function and homology information


cyclic GMP-AMP synthase / positive regulation of cGMP-mediated signaling / 2',3'-cyclic GMP-AMP synthase activity / regulation of type I interferon production / paracrine signaling / regulation of immunoglobulin production / negative regulation of double-strand break repair via homologous recombination / regulation of T cell activation / cellular response to exogenous dsRNA / positive regulation of cAMP-mediated signaling ...cyclic GMP-AMP synthase / positive regulation of cGMP-mediated signaling / 2',3'-cyclic GMP-AMP synthase activity / regulation of type I interferon production / paracrine signaling / regulation of immunoglobulin production / negative regulation of double-strand break repair via homologous recombination / regulation of T cell activation / cellular response to exogenous dsRNA / positive regulation of cAMP-mediated signaling / positive regulation of type I interferon production / negative regulation of megakaryocyte differentiation / Packaging Of Telomere Ends / Chromatin modifying enzymes / Cleavage of the damaged purine / Recognition and association of DNA glycosylase with site containing an affected purine / Deposition of new CENPA-containing nucleosomes at the centromere / regulation of immune response / DNA replication-independent chromatin assembly / Cleavage of the damaged pyrimidine / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Inhibition of DNA recombination at telomere / Meiotic synapsis / heterochromatin assembly => GO:0031507 / telomere organization / RNA Polymerase I Promoter Opening / SUMOylation of chromatin organization proteins / Interleukin-7 signaling / determination of adult lifespan / DNA replication-dependent chromatin assembly / DNA methylation / positive regulation of defense response to virus by host / innate immune response in mucosa / HCMV Late Events / SIRT1 negatively regulates rRNA expression / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / Condensation of Prophase Chromosomes / PRC2 methylates histones and DNA / activation of innate immune response / Defective pyroptosis / RNA Polymerase I Promoter Escape / HDACs deacetylate histones / nuclear chromosome / Transcriptional regulation by small RNAs / NoRC negatively regulates rRNA expression / Nonhomologous End-Joining (NHEJ) / phosphatidylinositol-4,5-bisphosphate binding / Formation of the beta-catenin:TCF transactivating complex / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / B-WICH complex positively regulates rRNA expression / DNA-templated transcription, initiation / Metalloprotease DUBs / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / DNA Damage/Telomere Stress Induced Senescence / G2/M DNA damage checkpoint / RMTs methylate histone arginines / nucleosome assembly / HCMV Early Events / HDMs demethylate histones / Pre-NOTCH Transcription and Translation / Meiotic recombination / PKMTs methylate histone lysines / nucleosome / Activation of anterior HOX genes in hindbrain development during early embryogenesis / UCH proteinases / Transcriptional regulation of granulopoiesis / site of double-strand break / positive regulation of cellular senescence / E3 ubiquitin ligases ubiquitinate target proteins / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / Processing of DNA double-strand break ends / Factors involved in megakaryocyte development and platelet production / HATs acetylate histones / double-stranded DNA binding / Senescence-Associated Secretory Phenotype (SASP) / defense response to virus / chromosome, telomeric region / Oxidative Stress Induced Senescence / antibacterial humoral response / Estrogen-dependent gene expression / antimicrobial humoral immune response mediated by antimicrobial peptide / Ub-specific processing proteases / defense response to Gram-positive bacterium / protein heterodimerization activity / Amyloid fiber formation / DNA repair / protein domain specific binding / cellular response to DNA damage stimulus / GTP binding / chromatin binding / innate immune response / enzyme binding / protein-containing complex / RNA binding / DNA binding / extracellular space / extracellular exosome / membrane / extracellular region
Similarity search - Function
Mab-21 domain / Mab-21 protein nucleotidyltransferase domain / Mab-21 / Histone H2B signature. / Histone H2B / Histone H2B / Histone H2A conserved site / Histone H2A signature. / Histone H2A, C-terminal domain / C-terminus of histone H2A ...Mab-21 domain / Mab-21 protein nucleotidyltransferase domain / Mab-21 / Histone H2B signature. / Histone H2B / Histone H2B / Histone H2A conserved site / Histone H2A signature. / Histone H2A, C-terminal domain / C-terminus of histone H2A / Histone 2A / Histone H2A / Histone H4, conserved site / Histone H4 signature. / Histone H4 / Histone H4 / Centromere kinetochore component CENP-T histone fold / CENP-T/Histone H4, histone fold / TATA box binding protein associated factor / TATA box binding protein associated factor (TAF) / Histone H3 signature 1. / Histone H3 signature 2. / Histone H3 / Histone H3/CENP-A / Core histone H2A/H2B/H3/H4 / Histone H2A/H2B/H3 / Histone-fold
Similarity search - Domain/homology
DNA (> 100) / DNA (> 10) / DNA / Histone H2A type 1 / Histone H4 / Histone H2B type 1-C/E/F/G/I / Histone H3.2 / Cyclic GMP-AMP synthase
Similarity search - Component
Biological speciesHomo sapiens (human)
synthetic construct (others)
Mus musculus (house mouse)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsBoyer, J.A. / Spangler, C.J. / Strauss, J.D. / Cesmat, A.P. / Liu, P. / McGinty, R.K. / Zhang, Q.
Funding support United States, 2items
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 guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS) recognizes cytosolic foreign or damaged DNA to activate the innate immune response to infection, inflammatory ...Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS) recognizes cytosolic foreign or damaged DNA to activate the innate immune response to infection, inflammatory diseases, and cancer. By 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 uses two conserved arginines to anchor to the nucleosome acidic patch. The nucleosome-binding interface exclusively occupies the strong double-stranded DNA (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.
History
DepositionAug 6, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 16, 2020Provider: repository / Type: Initial release
Revision 1.1Sep 23, 2020Group: Database references / Category: citation / citation_author
Item: _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID
Revision 1.2Nov 4, 2020Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-22408
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Histone H3.2
B: Histone H4
C: Histone H2A type 1
D: Histone H2B type 1-C/E/F/G/I
E: Histone H3.2
F: Histone H4
G: Histone H2A type 1
H: Histone H2B type 1-C/E/F/G/I
I: DNA (145-MER)
J: DNA (145-MER)
K: Cyclic GMP-AMP synthase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)243,02312
Polymers242,95711
Non-polymers651
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
d_1ens_1chain "C"
d_2ens_1chain "G"
d_1ens_2chain "D"
d_2ens_2chain "H"

NCS domain segments:
Dom-IDComponent-IDEns-IDBeg label comp-IDEnd label comp-IDLabel asym-IDLabel seq-ID
d_11ens_1ALALYSC1 - 109
d_21ens_1ALALYSG1 - 109
d_11ens_2ARGSERD1 - 94
d_21ens_2ARGSERH1 - 94

NCS ensembles :
ID
ens_1
ens_2

NCS oper:
IDCodeMatrixVector
1given(-0.782198487121, 0.107776460007, 0.613636505934), (0.12545719378, -0.937501718846, 0.324578218138), (0.610267170405, 0.330869705216, 0.719791093926)88.0017180491, 116.240035814, -53.5529209476
2given(-0.783796053679, 0.119271695636, 0.609457142757), (0.11531694032, -0.936362895529, 0.331551702079), (0.610217788591, 0.330149648639, 0.720163495319)87.8372289892, 116.147074605, -53.4920587354

-
Components

-
Protein , 5 types, 9 molecules AEBFCGDHK

#1: Protein Histone H3.2 / H3-clustered histone 13 / H3-clustered histone 14 / H3-clustered histone 15 / Histone H3/m / Histone H3/o


Mass: 15421.101 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human)
Gene: H3C15, HIST2H3A, H3C14, H3F2, H3FM, HIST2H3C, H3C13, HIST2H3D
Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): pLysS / References: UniProt: Q71DI3
#2: Protein Histone H4 /


Mass: 11394.426 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human)
Gene: HIST1H4A, H4/A, H4FA, HIST1H4B, H4/I, H4FI, HIST1H4C, H4/G, H4FG, HIST1H4D, H4/B, H4FB, HIST1H4E, H4/J, H4FJ, HIST1H4F, H4/C, H4FC, HIST1H4H, H4/H, H4FH, HIST1H4I, H4/M, H4FM, HIST1H4J, H4/E, ...Gene: HIST1H4A, H4/A, H4FA, HIST1H4B, H4/I, H4FI, HIST1H4C, H4/G, H4FG, HIST1H4D, H4/B, H4FB, HIST1H4E, H4/J, H4FJ, HIST1H4F, H4/C, H4FC, HIST1H4H, H4/H, H4FH, HIST1H4I, H4/M, H4FM, HIST1H4J, H4/E, H4FE, HIST1H4K, H4/D, H4FD, HIST1H4L, H4/K, H4FK, HIST2H4A, H4/N, H4F2, H4FN, HIST2H4, HIST2H4B, H4/O, H4FO, HIST4H4
Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): pLysS / References: UniProt: P62805
#3: Protein Histone H2A type 1 / H2A.1 / Histone H2A/ptl


Mass: 13990.342 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human)
Gene: H2AC11, H2AFP, HIST1H2AG, H2AC13, H2AFC, HIST1H2AI, H2AC15, H2AFD, HIST1H2AK, H2AC16, H2AFI, HIST1H2AL, H2AC17, H2AFN, HIST1H2AM
Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): pLysS / References: UniProt: P0C0S8
#4: Protein Histone H2B type 1-C/E/F/G/I / Histone H2B.1 A / Histone H2B.a / H2B/a / Histone H2B.g / H2B/g / Histone H2B.h / H2B/h / Histone ...Histone H2B.1 A / Histone H2B.a / H2B/a / Histone H2B.g / H2B/g / Histone H2B.h / H2B/h / Histone H2B.k / H2B/k / Histone H2B.l / H2B/l


Mass: 13806.018 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human)
Gene: H2BC4, H2BFL, HIST1H2BC, H2BC6, H2BFH, HIST1H2BE, H2BC7, H2BFG, HIST1H2BF, H2BC8, H2BFA, HIST1H2BG, H2BC10, H2BFK, HIST1H2BI
Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): pLysS / References: UniProt: P62807
#7: Protein Cyclic GMP-AMP synthase / / m-cGAS / 2'3'-cGAMP synthase / Mab-21 domain-containing protein 1


Mass: 42984.664 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Cgas, Mb21d1 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q8C6L5, cyclic GMP-AMP synthase

-
DNA chain , 2 types, 2 molecules IJ

#5: DNA chain DNA (145-MER)


Mass: 45610.043 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) synthetic construct (others) / Production host: Escherichia coli HB101 (bacteria)
#6: DNA chain DNA (145-MER)


Mass: 45138.770 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) synthetic construct (others) / Production host: Escherichia coli HB101 (bacteria)

-
Non-polymers , 1 types, 1 molecules

#8: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn

-
Details

Has ligand of interestN

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: 1:1 cGAS-nucleosome complex / Type: COMPLEX / Details: mouse cGAS bound to the nucleosome in a 1:1 ratio / Entity ID: #1-#7 / Source: MULTIPLE SOURCES
Molecular weightValue: 0.25 MDa / Experimental value: NO
Source (natural)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5
Buffer component
IDConc.NameFormulaBuffer-ID
120 mMHEPESC8H18N2O4S1
2150 mMsodium chlorideNaClSodium chloride1
31 mMTCEPC9H15O6P1
SpecimenConc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportDetails: Instrument: Pelco easiGlow / Grid material: COPPER / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 293 K

-
Electron microscopy imaging

Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company
MicroscopyModel: FEI TALOS ARCTICA
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy
Image recordingElectron dose: 53 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 2100

-
Processing

Software
NameVersionClassification
phenix.real_space_refine1.18_3861refinement
PHENIX1.18_3861refinement
EM software
IDNameVersionCategory
1RELION3.1-betaparticle selection
2SerialEMimage acquisition
4CTFFIND4.1CTF correction
7PHENIX1.18model fitting
9RELION3.1-betainitial Euler assignment
10RELION3.1-betafinal Euler assignment
11RELION3.1-betaclassification
12RELION3.1-beta3D reconstruction
19PHENIX1.18model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 433445
3D reconstructionResolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 116377 / Symmetry type: POINT
Atomic model buildingSpace: REAL
Atomic model building
IDPDB-ID 3D fitting-ID
16FQ51
24K8V1
RefinementCross valid method: NONE
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
Displacement parametersBiso mean: 50.17 Å2
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.007715861
ELECTRON MICROSCOPYf_angle_d0.729622634
ELECTRON MICROSCOPYf_chiral_restr0.04182547
ELECTRON MICROSCOPYf_plane_restr0.00511861
ELECTRON MICROSCOPYf_dihedral_angle_d27.07526473
Refine LS restraints NCS
Ens-IDDom-IDAuth asym-IDRefine-IDTypeRms dev position (Å)
ens_1d_2CELECTRON MICROSCOPYNCS constraints0.0061842386645
ens_2d_2DELECTRON MICROSCOPYNCS constraints0.000752970227663

+
About Yorodumi

-
News

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

-
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242):Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

+
Jun 16, 2017. Omokage search with filter

Omokage search with filter

Result of Omokage search can be filtered by keywords and the database types

Related info.:Omokage search

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more