PDB-6o8c: Crystal structure of STING CTT in complex with TBK1

ID or keywords:

Entry

Database: PDB / ID: 6o8c

Title

Crystal structure of STING CTT in complex with TBK1

Components

Serine/threonine-protein kinase TBK1
Stimulator of interferon genes protein

Keywords

IMMUNE SYSTEM /

Adaptor /

kinase /

Complex

Function / homology

Function and homology information

Interleukin-37 signaling / STAT6-mediated induction of chemokines / IRF3-mediated induction of type I IFN / DDX58/IFIH1-mediated induction of interferon-alpha/beta / TNFR1-induced proapoptotic signaling / Negative regulators of DDX58/IFIH1 signaling / Regulation of innate immune responses to cytosolic DNA / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Regulation of TNFR1 signaling / STING complex ...Interleukin-37 signaling / STAT6-mediated induction of chemokines / IRF3-mediated induction of type I IFN / DDX58/IFIH1-mediated induction of interferon-alpha/beta / TNFR1-induced proapoptotic signaling / Negative regulators of DDX58/IFIH1 signaling / Regulation of innate immune responses to cytosolic DNA / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Regulation of TNFR1 signaling / STING complex / STAT6-mediated induction of chemokines / positive regulation of xenophagy /

serine/threonine protein kinase complex /

proton channel activity / 2',3'-cyclic GMP-AMP binding / regulation of type I interferon production / dendritic cell proliferation / cyclic-di-GMP binding / STING mediated induction of host immune responses / cGAS/STING signaling pathway / IRF3-mediated induction of type I IFN / positive regulation of type I interferon-mediated signaling pathway / reticulophagy / toll-like receptor 4 signaling pathway / pattern recognition receptor signaling pathway / cellular response to exogenous dsRNA / cytoplasmic pattern recognition receptor signaling pathway / autophagosome membrane / positive regulation of interferon-alpha production / antiviral innate immune response / positive regulation of macroautophagy /

autophagosome assembly / cellular response to organic cyclic compound / positive regulation of type I interferon production /

autophagosome / cellular response to interferon-beta / signaling adaptor activity / positive regulation of autophagy / positive regulation of defense response to virus by host / negative regulation of TORC1 signaling / positive regulation of TORC1 signaling / Regulation of innate immune responses to cytosolic DNA / activation of innate immune response / positive regulation of interferon-beta production / endoplasmic reticulum-Golgi intermediate compartment membrane / secretory granule membrane /

phosphoprotein binding / peptidyl-threonine phosphorylation / cytoplasmic vesicle membrane /

peroxisome / SARS-CoV-1 activates/modulates innate immune responses / positive regulation of DNA-binding transcription factor activity / protein complex oligomerization / positive regulation of protein binding /

regulation of inflammatory response /

regulation of gene expression / defense response to virus /

protein phosphatase binding / peptidyl-serine phosphorylation / positive regulation of canonical NF-kappaB signal transduction / mitochondrial outer membrane / RNA polymerase II-specific DNA-binding transcription factor binding /

nucleic acid binding /

non-specific serine/threonine protein kinase /

endosome / defense response to Gram-positive bacterium /

Golgi membrane / negative regulation of gene expression /

protein phosphorylation /

innate immune response / protein serine kinase activity / intracellular membrane-bounded organelle / protein serine/threonine kinase activity /

ubiquitin protein ligase binding / Neutrophil degranulation / endoplasmic reticulum membrane /

protein kinase binding / SARS-CoV-2 activates/modulates innate and adaptive immune responses / perinuclear region of cytoplasm / protein homodimerization activity / positive regulation of transcription by RNA polymerase II /

nucleoplasm /

ATP binding / identical protein binding /

plasma membrane /

cytosol /

cytoplasm
Similarity search - Function

Biological species

Mus musculus (house mouse)

Homo sapiens (human)

Method

X-RAY DIFFRACTION /

SYNCHROTRON /

MOLECULAR REPLACEMENT / Resolution: 3.17 Å

Authors

Li, P. / Zhao, B. / Du, F.

Funding support

United States, 1items

Citation

Journal: Nature / Year: 2019
Title: A conserved PLPLRT/SD motif of STING mediates the recruitment and activation of TBK1.
Authors: Zhao, B. / Du, F. / Xu, P. / Shu, C. / Sankaran, B. / Bell, S.L. / Liu, M. / Lei, Y. / Gao, X. / Fu, X. / Zhu, F. / Liu, Y. / Laganowsky, A. / Zheng, X. / Ji, J.Y. / West, A.P. / Watson, R.O. / Li, P.

History

Deposition	Mar 9, 2019	Deposition site: RCSB / Processing site: RCSB
Revision 1.0	May 22, 2019	Provider: repository / Type: Initial release
Revision 1.1	Jun 5, 2019	Group: Data collection / Database references / Category: citation / citation_author Item: _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.name
Revision 1.2	Jun 12, 2019	Group: Data collection / Database references / Category: citation Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.3	Oct 11, 2023	Group: Data collection / Database references / Refinement description Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

Structure viewer	Molecule: MolmilJmol/JSmol

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PDBx/mmCIF format	6o8c.cif.gz	542.6 KB	Display	PDBx/mmCIF format
PDB format	pdb6o8c.ent.gz	455.2 KB	Display	PDB format
PDBx/mmJSON format	6o8c.json.gz		Tree view	PDBx/mmJSON format
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Validation report

Arichive directory	https://data.pdbj.org/pub/pdb/validation_reports/o8/6o8c ftp://data.pdbj.org/pub/pdb/validation_reports/o8/6o8c	HTTPS FTP

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Related structure data

Related structure data	6o8bC 4jlcS S: Starting model for refinement C: citing same article (ref.)
Similar structure data	4jlc-2 4jl9-2 30358 0095 3dmk-1 7jps-d Search similar-shape structures by Omokage search (details) Similarity search - Function & homologyF&H Search Similarity search - FunctionF&H Search Similarity search - HomologyF&H Search

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Links

PDB pages	PDBj / wwPDB / NCBI
Related items in Molecule of the Month	#122 - Feb 2010 Enhanceosome similarity (2) #55 - Jul 2004 DNA Ligase similarity (1) #60 - Dec 2004 Ubiquitin similarity (1) #234 - Jun 2019 MDM2 and Cancer similarity (1)

Deposited unit

A: Serine/threonine-protein kinase TBK1

B: Serine/threonine-protein kinase TBK1

D: Stimulator of interferon genes protein

E: Stimulator of interferon genes protein

hetero molecules

162 kDa, 4 polymers
Search similar-shape structures of this assembly by Omokage search (details)

1

Idetical with deposited unit
defined by author&software
Evidence: surface plasmon resonance

Unit cell

Length a, b, c (Å)	249.510, 249.510, 243.783
Angle α, β, γ (deg.)	90.00, 90.00, 120.00
Int Tables number	179
Space group name H-M	P6₅22

#1: Protein	Serine/threonine-protein kinase TBK1 / T2K / TANK-binding kinase 1 Mass: 76359.070 Da / Num. of mol.: 2 / Mutation: S172A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Tbk1 / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: Q9WUN2, non-specific serine/threonine protein kinase
#2: Protein/peptide	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: 4213.761 Da / Num. of mol.: 2 / Mutation: V343W Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: TMEM173, ERIS, MITA, STING / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) / References: UniProt: Q86WV6
#3: Chemical	ChemComp-BX7 / N-(3-{[5-iodo-4-({3-[(thiophen-2-ylcarbonyl)amino]propyl}amino)pyrimidin-2-yl]amino}phenyl)pyrrolidine-1-carboxamide Mass: 591.468 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C₂₃H₂₆IN₇O₂S

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Experiment

Experiment	Method: X-RAY DIFFRACTION / Number of used crystals: 1

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Sample preparation

Crystal	Density Matthews: 6.8 Å³/Da / Density % sol: 81.9 %
Crystal grow	Temperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7 Details: 18% v/v tacsimate pH 7.0, 0.1 M HEPES pH 7.0, 2% PEG3350

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Data collection

Diffraction	Mean temperature: 120 K / Serial crystal experiment: N
Diffraction source	Source: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å
Detector	Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Apr 15, 2017
Radiation	Monochromator: Double-crystal, Si (111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelength	Wavelength: 1 Å / Relative weight: 1
Reflection	Resolution: 3.17→81.671 Å / Num. obs: 76001 / % possible obs: 100 % / Redundancy: 12.3 % / R_merge(I) obs: 0.184 / R_pim(I) all: 0.054 / Net I/σ(I): 13.8
Reflection shell	Resolution: 3.17→3.24 Å / Redundancy: 11.3 % / R_merge(I) obs: 2.7 / Num. unique obs: 4418 / R_pim(I) all: 0.85 / % possible all: 100

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Processing

Software

Name	Version	Classification
PHENIX	(1.13_2998: ???)	refinement
iMOSFLM		data reduction
pointless		data scaling
PHENIX		phasing

Refinement

Method to determine structure:

MOLECULAR REPLACEMENT
Starting model: 4JLC

4jlc

Resolution: 3.17→81.671 Å / SU ML: 0.45 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 24.8

	R_factor	Num. reflection	% reflection
R_free	0.2305	3720	4.9 %
R_work	0.2135	-	-
obs	0.2143	75886	99.93 %

Solvent computation

Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å

Refinement step

Cycle: LAST / Resolution: 3.17→81.671 Å

	Protein	Nucleic acid	Ligand	Solvent	Total
Num. atoms	10527	0	68	0	10595

Refine LS restraints

Refine-ID	Type	Dev ideal	Number
X-RAY DIFFRACTION	f_bond_d	0.012	10830
X-RAY DIFFRACTION	f_angle_d	1.086	14616
X-RAY DIFFRACTION	f_dihedral_angle_d	17.413	6529
X-RAY DIFFRACTION	f_chiral_restr	0.054	1610
X-RAY DIFFRACTION	f_plane_restr	0.005	1863

LS refinement shell

Resolution (Å)	R_factor R_free	Num. reflection R_free	R_factor R_work	Num. reflection R_work	Refine-ID	% reflection obs (%)
3.17-3.2101	0.4267	156	0.3844	2596	X-RAY DIFFRACTION	100
3.2101-3.2524	0.3968	117	0.3502	2649	X-RAY DIFFRACTION	100
3.2524-3.2969	0.3439	148	0.3298	2617	X-RAY DIFFRACTION	100
3.2969-3.344	0.3502	130	0.3239	2632	X-RAY DIFFRACTION	100
3.344-3.394	0.3396	151	0.2981	2626	X-RAY DIFFRACTION	100
3.394-3.447	0.3306	113	0.289	2660	X-RAY DIFFRACTION	100
3.447-3.5035	0.3315	150	0.2808	2618	X-RAY DIFFRACTION	100
3.5035-3.5639	0.3085	131	0.2749	2660	X-RAY DIFFRACTION	100
3.5639-3.6287	0.3175	146	0.2747	2638	X-RAY DIFFRACTION	100
3.6287-3.6985	0.2894	122	0.2641	2642	X-RAY DIFFRACTION	100
3.6985-3.774	0.2305	146	0.248	2636	X-RAY DIFFRACTION	100
3.774-3.8561	0.2599	131	0.2338	2639	X-RAY DIFFRACTION	100
3.8561-3.9458	0.2553	132	0.2145	2662	X-RAY DIFFRACTION	100
3.9458-4.0444	0.232	139	0.2184	2652	X-RAY DIFFRACTION	100
4.0444-4.1538	0.2165	142	0.2114	2647	X-RAY DIFFRACTION	100
4.1538-4.276	0.2207	150	0.1978	2650	X-RAY DIFFRACTION	100
4.276-4.414	0.2253	139	0.1926	2664	X-RAY DIFFRACTION	100
4.414-4.5718	0.2045	109	0.193	2678	X-RAY DIFFRACTION	100
4.5718-4.7548	0.2157	147	0.1971	2668	X-RAY DIFFRACTION	100
4.7548-4.9712	0.1904	163	0.1871	2657	X-RAY DIFFRACTION	100
4.9712-5.2332	0.2134	149	0.1851	2660	X-RAY DIFFRACTION	100
5.2332-5.561	0.2217	120	0.1984	2712	X-RAY DIFFRACTION	100
5.561-5.9903	0.2255	114	0.2246	2740	X-RAY DIFFRACTION	100
5.9903-6.5929	0.2412	140	0.2257	2723	X-RAY DIFFRACTION	100
6.5929-7.5463	0.2499	146	0.2098	2725	X-RAY DIFFRACTION	100
7.5463-9.5052	0.1595	150	0.1568	2774	X-RAY DIFFRACTION	100
9.5052-81.6984	0.1652	139	0.1693	2941	X-RAY DIFFRACTION	99

Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

ID	L11 (°²)	L12 (°²)	L13 (°²)	L22 (°²)	L23 (°²)	L33 (°²)	S11 (Å °)	S12 (Å °)	S13 (Å °)	S21 (Å °)	S22 (Å °)	S23 (Å °)	S31 (Å °)	S32 (Å °)	S33 (Å °)	T11 (Å²)	T12 (Å²)	T13 (Å²)	T22 (Å²)	T23 (Å²)	T33 (Å²)	Origin x (Å)	Origin y (Å)	Origin z (Å)
1	1.8878	1.9431	-0.244	7.2156	-1.6896	2.9044	-0.1361	-0.3921	-0.1761	0.3736	-0.1279	-0.1964	-0.1503	0.1537	0.2628	0.8749	0.1839	0.0761	0.7004	0.0083	0.4344	118.1298	-52.4947	7.4187
2	1.5174	-1.0493	0.7177	2.3678	-1.4635	0.9523	-0.7154	-0.8341	-0.0173	0.3619	0.0825	-0.5917	-0.4414	0.0788	0.5107	1.1957	0.2436	-0.0996	0.9915	0.0919	0.6939	133.3568	-42.8482	17.4736
3	2.6136	-0.7691	-0.665	4.3627	-0.9599	3.0571	-0.2707	-0.5117	0.2808	0.7081	0.0862	-0.2173	-1.2658	0.1237	0.1552	1.3527	0.0297	-0.1497	0.5379	-0.1365	0.5141	124.3313	-21.0931	1.6682
4	2.1831	-3.8733	-0.3042	9.3965	0.3805	0.235	0.0262	-0.0116	0.3556	-0.5752	-0.0239	-0.0434	-0.275	0.0054	-0.0027	1.3026	0.0631	-0.1741	0.5789	-0.0685	0.7072	117.2164	-9.9157	-21.4139
5	5.8512	-2.1392	-0.3051	2.0251	0.5323	0.9959	-0.0176	0.4545	-0.3069	-0.6773	-0.1565	0.0582	-0.1119	0.0031	0.1894	1.3304	0.1115	-0.0821	0.6361	-0.0998	0.5118	117.6257	-55.211	-42.6698
6	0.5992	0.3741	0.4138	2.9219	2.9916	3.1363	-0.4956	0.2806	0.0623	-0.4645	0.1343	0.5351	-0.4503	-0.1257	0.3799	1.3548	0.1481	-0.2496	0.8147	-0.1541	0.7575	104.3694	-57.0736	-51.3541
7	2.1045	0.1333	-0.8817	4.4129	1.4486	3.2784	-0.0694	0.4155	-0.0737	-1.0037	-0.2648	0.6354	-0.7277	-0.7673	0.2822	1.2689	0.297	-0.5088	0.8133	-0.1031	0.9249	92.1588	-37.2448	-40.8044
8	0.9564	-1.0828	0.2747	5.7451	-1.2399	1.6581	-0.3307	-0.1389	0.309	0.3032	0.4062	0.6685	-0.6158	-0.4802	-0.1479	1.0786	0.3436	-0.27	0.7533	-0.1239	1.054	89.1391	-17.9664	-16.3848
9	2.7369	-2.365	0.5599	2.2365	-1.4152	6.9216	0.5844	0.0707	-0.2719	-1.7812	0.12	-1.4723	0.0577	1.702	-0.9657	1.4174	0.1667	0.1002	0.9913	-0.1391	0.9374	140.7469	-58.0658	-31.8834
10	5.5387	2.279	-4.3203	6.4131	0.1203	4.02	1.0276	3.0324	-2.8498	-0.0616	-0.0974	1.0951	1.5967	-0.6124	-0.6949	1.4846	-0.1738	-0.3002	1.0422	-0.2328	1.0335	103.0702	-71.9549	-2.7147

Refinement TLS group

ID	Refine-ID	Refine TLS-ID	Selection details
1	X-RAY DIFFRACTION	1	chain 'A' and (resid -4 through 145 )
2	X-RAY DIFFRACTION	2	chain 'A' and (resid 146 through 216 )
3	X-RAY DIFFRACTION	3	chain 'A' and (resid 217 through 369 )
4	X-RAY DIFFRACTION	4	chain 'A' and (resid 370 through 651 )
5	X-RAY DIFFRACTION	5	chain 'B' and (resid -3 through 128 )
6	X-RAY DIFFRACTION	6	chain 'B' and (resid 129 through 188 )
7	X-RAY DIFFRACTION	7	chain 'B' and (resid 189 through 369 )
8	X-RAY DIFFRACTION	8	chain 'B' and (resid 370 through 653 )
9	X-RAY DIFFRACTION	9	chain 'D' and (resid 366 through 379 )
10	X-RAY DIFFRACTION	10	chain 'E' and (resid 368 through 379 )

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