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- PDB-8a2j: human STING in complex with 2'-3'-cyclic-GMP-7-deaza(4-biphenylyl)-AMP -

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Basic information

Entry
Database: PDB / ID: 8a2j
Titlehuman STING in complex with 2'-3'-cyclic-GMP-7-deaza(4-biphenylyl)-AMP
ComponentsStimulator of interferon genes protein
KeywordsIMMUNE SYSTEM / Complex / STING / cyclic dinucleotide
Function / homology
Function and homology information


STING complex / STAT6-mediated induction of chemokines / protein localization to endoplasmic reticulum / 2',3'-cyclic GMP-AMP binding / cyclic-di-GMP binding / STING mediated induction of host immune responses / serine/threonine protein kinase complex / positive regulation of type I interferon-mediated signaling pathway / IRF3-mediated induction of type I IFN / proton channel activity ...STING complex / STAT6-mediated induction of chemokines / protein localization to endoplasmic reticulum / 2',3'-cyclic GMP-AMP binding / cyclic-di-GMP binding / STING mediated induction of host immune responses / serine/threonine protein kinase complex / positive regulation of type I interferon-mediated signaling pathway / IRF3-mediated induction of type I IFN / proton channel activity / cGAS/STING signaling pathway / reticulophagy / pattern recognition receptor signaling pathway / cytoplasmic pattern recognition receptor signaling pathway / cellular response to exogenous dsRNA / protein complex oligomerization / positive regulation of macroautophagy / autophagosome membrane / autophagosome assembly / positive regulation of type I interferon production / cellular response to interferon-beta / signaling adaptor activity / positive regulation of defense response to virus by host / antiviral innate immune response / endoplasmic reticulum-Golgi intermediate compartment membrane / activation of innate immune response / cytoplasmic vesicle membrane / Regulation of innate immune responses to cytosolic DNA / autophagosome / positive regulation of interferon-beta production / positive regulation of DNA-binding transcription factor activity / secretory granule membrane / SARS-CoV-1 activates/modulates innate immune responses / positive regulation of protein binding / peroxisome / regulation of inflammatory response / defense response to virus / RNA polymerase II-specific DNA-binding transcription factor binding / mitochondrial outer membrane / endosome / ciliary basal body / cilium / Golgi membrane / innate immune response / ubiquitin protein ligase binding / Neutrophil degranulation / endoplasmic reticulum membrane / protein kinase binding / perinuclear region of cytoplasm / SARS-CoV-2 activates/modulates innate and adaptive immune responses / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / nucleoplasm / identical protein binding / plasma membrane / cytosol
Similarity search - Function
: / STING transmembrane domain / : / : / Stimulator of interferon genes protein / Stimulator of interferon genes protein, C-terminal domain superfamily / STING ligand-binding domain
Similarity search - Domain/homology
Chem-KWO / Stimulator of interferon genes protein
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.32 Å
AuthorsVavrina, Z. / Brynda, J. / Rezacova, P.
Funding supportEuropean Union, 1items
OrganizationGrant numberCountry
European Regional Development FundCZ.02.1.01/0.0/0.0/16_019/0000729European Union
CitationJournal: J.Med.Chem. / Year: 2022
Title: Design, Synthesis, and Biochemical and Biological Evaluation of Novel 7-Deazapurine Cyclic Dinucleotide Analogues as STING Receptor Agonists.
Authors: Vavrina, Z. / Perlikova, P. / Milisavljevic, N. / Chevrier, F. / Smola, M. / Smith, J. / Dejmek, M. / Havlicek, V. / Budesinsky, M. / Liboska, R. / Vanekova, L. / Brynda, J. / Boura, E. / ...Authors: Vavrina, Z. / Perlikova, P. / Milisavljevic, N. / Chevrier, F. / Smola, M. / Smith, J. / Dejmek, M. / Havlicek, V. / Budesinsky, M. / Liboska, R. / Vanekova, L. / Brynda, J. / Boura, E. / Rezacova, P. / Hocek, M. / Birkus, G.
History
DepositionJun 3, 2022Deposition site: PDBE / Processing site: PDBE
Revision 1.0Oct 12, 2022Provider: repository / Type: Initial release
Revision 1.1Oct 19, 2022Group: Database references / Category: citation / citation_author / Item: _citation.pdbx_database_id_PubMed / _citation.title
Revision 1.2Nov 9, 2022Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.3Jan 31, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model / struct_ncs_dom_lim
Item: _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id ..._struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Stimulator of interferon genes protein
B: Stimulator of interferon genes protein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)55,0213
Polymers54,1952
Non-polymers8261
Water1,65792
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)94.290, 116.910, 35.980
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP21212
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11(chain A and ((resid 153 and (name N or name...
21(chain B and (resid 153 through 173 or (resid 174...

NCS domain segments:

Ens-ID: 1

Dom-IDComponent-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDSelection detailsAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11PHEPHEPHEPHE(chain A and ((resid 153 and (name N or name...AA15315
12GLYGLYGLUGLU(chain A and ((resid 153 and (name N or name...AA151 - 33713 - 199
13GLYGLYGLUGLU(chain A and ((resid 153 and (name N or name...AA151 - 33713 - 199
14GLYGLYGLUGLU(chain A and ((resid 153 and (name N or name...AA151 - 33713 - 199
15GLYGLYGLUGLU(chain A and ((resid 153 and (name N or name...AA151 - 33713 - 199
21PHEPHEPROPRO(chain B and (resid 153 through 173 or (resid 174...BB153 - 17315 - 35
22GLUGLUGLUGLU(chain B and (resid 153 through 173 or (resid 174...BB17436
23PHEPHEGLUGLU(chain B and (resid 153 through 173 or (resid 174...BB153 - 33715 - 199
24PHEPHEGLUGLU(chain B and (resid 153 through 173 or (resid 174...BB153 - 33715 - 199
25PHEPHEGLUGLU(chain B and (resid 153 through 173 or (resid 174...BB153 - 33715 - 199
26PHEPHEGLUGLU(chain B and (resid 153 through 173 or (resid 174...BB153 - 33715 - 199

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Components

#1: Protein Stimulator of interferon genes protein / hSTING / Endoplasmic reticulum interferon stimulator / ERIS / Mediator of IRF3 activation / hMITA / ...hSTING / Endoplasmic reticulum interferon stimulator / ERIS / Mediator of IRF3 activation / hMITA / Transmembrane protein 173


Mass: 27097.514 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: STING1, ERIS, MITA, STING, TMEM173 / Production host: Escherichia coli (E. coli) / References: UniProt: Q86WV6
#2: Chemical ChemComp-KWO / 2-azanyl-9-[(1~{R},6~{R},8~{R},9~{R},10~{S},15~{R},17~{R},18~{R})-8-[4-azanyl-5-(4-phenylphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]-3,9,12,18-tetrakis(oxidanyl)-3,12-bis(oxidanylidene)-2,4,7,11,13,16-hexaoxa-3$l^{5},12$l^{5}-diphosphatricyclo[13.2.1.0^{6,10}]octadecan-17-yl]-1~{H}-purin-6-one / 2-azanyl-9-[(1~{R},6~{R},8~{R},9~{R},10~{S},15~{R},17~{R},18~{R})-8-[4-azanyl-5-(4-phenylphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]-3,9,12,18-tetrakis(oxidanyl)-3,12-bis(oxidanylidene)-2,4,7,11,13,16-hexaoxa-3$l^{5},12$l^{5}-diphosphatricyclo[13.2.1.0^{6,10}]octadecan-17-yl]-1~{H}-purin-6-one


Mass: 825.615 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C33H33N9O13P2 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 92 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

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Experimental details

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Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop / Details: 100 mM citric acid, 20% (w/v) PEG 6000

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.54 Å
DetectorType: DECTRIS PILATUS 200K / Detector: PIXEL / Date: Oct 5, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54 Å / Relative weight: 1
ReflectionResolution: 2.32→36.02 Å / Num. obs: 21423 / % possible obs: 95.2 % / Redundancy: 5.417 % / Biso Wilson estimate: 33.9 Å2 / CC1/2: 0.993 / Rmerge(I) obs: 0.193 / Rrim(I) all: 0.213 / Χ2: 0.787 / Net I/σ(I): 6.7
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured obsNum. possibleNum. unique obsCC1/2Rrim(I) all% possible all
2.45-2.64.8051.8690.799888244020580.5262.07784.3
2.6-2.785.1671.1211.3811115229921510.71.24293.6
2.78-35.5870.6872.2711521213720620.8720.75996.5
3-3.295.9310.3544.4311648198219640.940.38899.1
3.29-3.676.0570.2297.5610666178417610.9750.25198.7
3.67-4.245.6810.15211.758954160715760.9850.16798.1
4.24-5.184.3240.10214.635889139813620.9920.11697.4
5.18-7.285.6030.13512.496119109910920.9880.14999.4
7.28-36.025.6930.05822.9836896656480.9980.06397.4

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Processing

Software
NameVersionClassification
XDSdata reduction
XSCALEdata scaling
PHENIX1.19.2_4158refinement
PDB_EXTRACT3.27data extraction
PHASER2.8.3phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4KSY

4ksy


Resolution: 2.32→36.02 Å / SU ML: 0.31 / Cross valid method: THROUGHOUT / σ(F): 1.37 / Phase error: 23.81 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.264 888 4.98 %
Rwork0.2245 16932 -
obs0.2264 17820 99.1 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 101.68 Å2 / Biso mean: 54.453 Å2 / Biso min: 30.27 Å2
Refinement stepCycle: final / Resolution: 2.32→36.02 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2767 0 57 92 2916
Biso mean--51.88 55.8 -
Num. residues----364
Refine LS restraints NCS
Ens-IDDom-IDAuth asym-IDNumberRefine-IDRmsType
11A1437X-RAY DIFFRACTION12.049TORSIONAL
12B1437X-RAY DIFFRACTION12.049TORSIONAL
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 6

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.32-2.470.29691410.23252722286397
2.47-2.660.32251410.23592748288998
2.66-2.920.31971510.243227952946100
2.92-3.350.25171460.210228182964100
3.35-4.210.25451560.204228473003100
4.21-36.020.23581530.23683002315599

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