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- PDB-5hyj: 1E6 TCR in Complex with HLA-A02 carrying AQWGPDPAAA -

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Basic information

Entry
Database: PDB / ID: 5hyj
Title1E6 TCR in Complex with HLA-A02 carrying AQWGPDPAAA
Components
  • (Human T-cell Receptor, Class I, ...) x 2
  • ALA-GLN-TRP-GLY-PRO-ASP-PRO-ALA-ALA-ALA
  • Beta-2-microglobulin
  • HLA class I histocompatibility antigen, A-2 alpha chain
KeywordsIMMUNE SYSTEM / IMMUNO / HLA-A02 / 1E6-TCR / Cross-reactivity
Function / homology
Function and homology information


T cell mediated cytotoxicity directed against tumor cell target / T cell receptor complex / positive regulation of memory T cell activation / negative regulation of NAD(P)H oxidase activity / negative regulation of glycogen catabolic process / regulation of cellular amino acid metabolic process / TAP complex binding / positive regulation of CD8-positive, alpha-beta T cell activation / CD8-positive, alpha-beta T cell activation / positive regulation of nitric oxide mediated signal transduction ...T cell mediated cytotoxicity directed against tumor cell target / T cell receptor complex / positive regulation of memory T cell activation / negative regulation of NAD(P)H oxidase activity / negative regulation of glycogen catabolic process / regulation of cellular amino acid metabolic process / TAP complex binding / positive regulation of CD8-positive, alpha-beta T cell activation / CD8-positive, alpha-beta T cell activation / positive regulation of nitric oxide mediated signal transduction / Golgi medial cisterna / negative regulation of fatty acid metabolic process / positive regulation of CD8-positive, alpha-beta T cell proliferation / negative regulation of feeding behavior / Signaling by Insulin receptor / CD8 receptor binding / IRS activation / Insulin processing / regulation of protein secretion / positive regulation of respiratory burst / positive regulation of peptide hormone secretion / antigen processing and presentation of exogenous peptide antigen via MHC class I / endoplasmic reticulum exit site / Regulation of gene expression in beta cells / negative regulation of acute inflammatory response / alpha-beta T cell activation / antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent / negative regulation of respiratory burst involved in inflammatory response / TAP binding / positive regulation of dendritic spine maintenance / protection from natural killer cell mediated cytotoxicity / positive regulation of glycogen biosynthetic process / Synthesis, secretion, and deacylation of Ghrelin / negative regulation of protein secretion / regulation of protein localization to plasma membrane / fatty acid homeostasis / Signal attenuation / beta-2-microglobulin binding / negative regulation of lipid catabolic process / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / negative regulation of gluconeogenesis / COPI-mediated anterograde transport / T cell receptor binding / positive regulation of lipid biosynthetic process / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / negative regulation of reactive oxygen species biosynthetic process / detection of bacterium / positive regulation of insulin receptor signaling pathway / nitric oxide-cGMP-mediated signaling / transport vesicle / positive regulation of protein autophosphorylation / Insulin receptor recycling / neuron projection maintenance / NPAS4 regulates expression of target genes / positive regulation of protein metabolic process / positive regulation of brown fat cell differentiation / positive regulation of glycolytic process / activation of protein kinase B activity / endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of mitotic nuclear division / Insulin receptor signalling cascade / positive regulation of ferrous iron binding / positive regulation of transferrin receptor binding / positive regulation of receptor binding / early endosome lumen / positive regulation of nitric-oxide synthase activity / Nef mediated downregulation of MHC class I complex cell surface expression / DAP12 interactions / negative regulation of receptor binding / positive regulation of cytokine production / positive regulation of long-term synaptic potentiation / acute-phase response / Regulation of insulin secretion / endosome lumen / antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent / antigen processing and presentation of endogenous peptide antigen via MHC class Ib / positive regulation of protein secretion / positive regulation of glucose import / negative regulation of proteolysis / lumenal side of endoplasmic reticulum membrane / cellular response to iron ion / positive regulation of cell differentiation / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / regulation of transmembrane transporter activity / insulin-like growth factor receptor binding / cellular response to iron(III) ion / wound healing / antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent / negative regulation of forebrain neuron differentiation / insulin receptor binding / regulation of synaptic plasticity / regulation of erythrocyte differentiation / ER to Golgi transport vesicle membrane / peptide antigen assembly with MHC class I protein complex / regulation of iron ion transport / response to molecule of bacterial origin / MHC class I peptide loading complex / HFE-transferrin receptor complex / negative regulation of protein catabolic process
Similarity search - Function
Insulin / Insulin family / Insulin/IGF/Relaxin family / Insulin, conserved site / Insulin family signature. / Insulin-like / Insulin / insulin-like growth factor / relaxin family. / Insulin-like superfamily / MHC class I, alpha chain, C-terminal / MHC_I C-terminus ...Insulin / Insulin family / Insulin/IGF/Relaxin family / Insulin, conserved site / Insulin family signature. / Insulin-like / Insulin / insulin-like growth factor / relaxin family. / Insulin-like superfamily / MHC class I, alpha chain, C-terminal / MHC_I C-terminus / MHC class I-like antigen recognition-like / Murine Class I Major Histocompatibility Complex, H2-DB; Chain A, domain 1 / MHC class I alpha chain, alpha1 alpha2 domains / Class I Histocompatibility antigen, domains alpha 1 and 2 / Immunoglobulin V-Type / Beta-2-Microglobulin / MHC class I-like antigen recognition-like / MHC class I-like antigen recognition-like superfamily / Immunoglobulin V-set domain / MHC classes I/II-like antigen recognition protein / Immunoglobulin V-set domain / Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin C-Type / Immunoglobulin C1-set / Immunoglobulin C1-set domain / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulins / Immunoglobulin-like fold / Immunoglobulin-like / Sandwich / 2-Layer Sandwich / Mainly Beta / Alpha Beta
Similarity search - Domain/homology
T cell receptor alpha variable 12-3 / T cell receptor beta variable 12-4 / Insulin / HLA class I histocompatibility antigen, A alpha chain / HLA class I histocompatibility antigen, A alpha chain / Beta-2-microglobulin
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.06 Å
AuthorsRizkallah, P.J. / Bulek, A.M. / Cole, D.K. / Sewell, A.K.
CitationJournal: J.Clin.Invest. / Year: 2016
Title: A "hotspot" for autoimmune T cells in type 1 diabetes.
Authors: Stadinski, B.D. / Obst, R. / Huseby, E.S.
History
DepositionFeb 1, 2016Deposition site: RCSB / Processing site: PDBE
Revision 1.0May 4, 2016Provider: repository / Type: Initial release
Revision 1.1May 25, 2016Group: Database references
Revision 1.2Jun 8, 2016Group: Database references
Revision 1.3Jan 10, 2024Group: 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 / struct_ncs_dom_lim
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _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: HLA class I histocompatibility antigen, A-2 alpha chain
B: Beta-2-microglobulin
C: ALA-GLN-TRP-GLY-PRO-ASP-PRO-ALA-ALA-ALA
D: Human T-cell Receptor, Class I, Light alpha Chain
E: Human T-cell Receptor, Class I, Heavy beta Chain
F: HLA class I histocompatibility antigen, A-2 alpha chain
G: Beta-2-microglobulin
H: ALA-GLN-TRP-GLY-PRO-ASP-PRO-ALA-ALA-ALA
I: Human T-cell Receptor, Class I, Light alpha Chain
J: Human T-cell Receptor, Class I, Heavy beta Chain


Theoretical massNumber of molelcules
Total (without water)189,06410
Polymers189,06410
Non-polymers00
Water1,47782
1
A: HLA class I histocompatibility antigen, A-2 alpha chain
B: Beta-2-microglobulin
C: ALA-GLN-TRP-GLY-PRO-ASP-PRO-ALA-ALA-ALA
D: Human T-cell Receptor, Class I, Light alpha Chain
E: Human T-cell Receptor, Class I, Heavy beta Chain


Theoretical massNumber of molelcules
Total (without water)94,5325
Polymers94,5325
Non-polymers00
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
F: HLA class I histocompatibility antigen, A-2 alpha chain
G: Beta-2-microglobulin
H: ALA-GLN-TRP-GLY-PRO-ASP-PRO-ALA-ALA-ALA
I: Human T-cell Receptor, Class I, Light alpha Chain
J: Human T-cell Receptor, Class I, Heavy beta Chain


Theoretical massNumber of molelcules
Total (without water)94,5325
Polymers94,5325
Non-polymers00
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)41.440, 97.310, 121.370
Angle α, β, γ (deg.)97.290, 97.660, 92.730
Int Tables number1
Space group name H-MP1
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21F
12B
22G
13D
23I
14E
24J

NCS domain segments:

Component-ID: _ / Refine code: _

Dom-IDEns-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11GLYGLYPROPROAA1 - 2761 - 276
21GLYGLYPROPROFF1 - 2761 - 276
12METMETMETMETBB0 - 991 - 100
22METMETMETMETGG0 - 991 - 100
13LYSLYSPROPRODD2 - 1941 - 193
23LYSLYSPROPROII2 - 1941 - 193
14ASPASPASPASPEE1 - 2461 - 246
24ASPASPASPASPJJ1 - 2461 - 246

NCS ensembles :
ID
1
2
3
4

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Components

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Protein , 2 types, 4 molecules AFBG

#1: Protein HLA class I histocompatibility antigen, A-2 alpha chain / MHC class I antigen A*2


Mass: 31951.316 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HLA-A, HLAA / Production host: Escherichia coli (E. coli) / References: UniProt: P01892, UniProt: P04439*PLUS
#2: Protein Beta-2-microglobulin


Mass: 11879.356 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: B2M, CDABP0092, HDCMA22P / Production host: Escherichia coli (E. coli) / References: UniProt: P61769

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Human T-cell Receptor, Class I, ... , 2 types, 4 molecules DIEJ

#4: Protein Human T-cell Receptor, Class I, Light alpha Chain


Mass: 21692.102 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) / References: UniProt: A0A0B4J271*PLUS
#5: Protein Human T-cell Receptor, Class I, Heavy beta Chain


Mass: 28026.434 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) / References: UniProt: A0A0B4J2E0*PLUS

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Protein/peptide / Non-polymers , 2 types, 84 molecules CH

#3: Protein/peptide ALA-GLN-TRP-GLY-PRO-ASP-PRO-ALA-ALA-ALA


Mass: 983.034 Da / Num. of mol.: 2 / Source method: obtained synthetically / Details: Occurs in humans / Source: (synth.) Homo sapiens (human) / References: UniProt: P01308*PLUS
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 82 / Source method: isolated from a natural source / Formula: H2O

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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

CrystalDensity Matthews: 2.54 Å3/Da / Density % sol: 51.56 %
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop / pH: 6.5
Details: 0.2M sodium citrate, 0.1M BIS TRIS propane pH6.5, 20% PEG 3350

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04-1 / Wavelength: 0.91731 Å
DetectorType: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Oct 1, 2010
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.91731 Å / Relative weight: 1
ReflectionResolution: 3.06→38.63 Å / Num. obs: 34039 / % possible obs: 97.2 % / Redundancy: 2.2 % / Rmerge(I) obs: 0.091 / Net I/σ(I): 5.7
Reflection shellResolution: 3.06→3.14 Å / Rmerge(I) obs: 0.27

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Processing

Software
NameVersionClassification
REFMAC5.8.0135refinement
PDB_EXTRACT3.2data extraction
XDSdata reduction
SCALAdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3UTQ, 3UTP
Resolution: 3.06→38.63 Å / Cor.coef. Fo:Fc: 0.909 / Cor.coef. Fo:Fc free: 0.821 / SU B: 67.35 / SU ML: 0.552 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.594
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.2935 1726 5.1 %RANDOM
Rwork0.2117 ---
obs0.2159 32310 97.19 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 187.1 Å2 / Biso mean: 72.831 Å2 / Biso min: 21.17 Å2
Baniso -1Baniso -2Baniso -3
1-1.01 Å2-0.1 Å25.69 Å2
2--1.14 Å23.09 Å2
3----4.31 Å2
Refinement stepCycle: final / Resolution: 3.06→38.63 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms13310 0 0 82 13392
Biso mean---44.37 -
Num. residues----1650
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0170.01913686
X-RAY DIFFRACTIONr_bond_other_d0.0060.0212332
X-RAY DIFFRACTIONr_angle_refined_deg2.0241.9318574
X-RAY DIFFRACTIONr_angle_other_deg1.507328418
X-RAY DIFFRACTIONr_dihedral_angle_1_deg9.39551640
X-RAY DIFFRACTIONr_dihedral_angle_2_deg38.17723.704702
X-RAY DIFFRACTIONr_dihedral_angle_3_deg21.968152220
X-RAY DIFFRACTIONr_dihedral_angle_4_deg20.85415102
X-RAY DIFFRACTIONr_chiral_restr0.1140.21922
X-RAY DIFFRACTIONr_gen_planes_refined0.0090.02115616
X-RAY DIFFRACTIONr_gen_planes_other0.0060.023354
X-RAY DIFFRACTIONr_mcbond_it1.9793.5636590
X-RAY DIFFRACTIONr_mcbond_other1.9753.5616589
X-RAY DIFFRACTIONr_mcangle_it3.4195.3348220
Refine LS restraints NCS

Refine-ID: X-RAY DIFFRACTION / Type: interatomic distance / Weight position: 0.05

Ens-IDDom-IDAuth asym-IDNumberRms dev position (Å)
11A300300.11
12F300300.11
21B114440.1
22G114440.1
31D192200.14
32I192200.14
41E277800.1
42J277800.1
LS refinement shellResolution: 3.063→3.142 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.351 130 -
Rwork0.275 2413 -
all-2543 -
obs--97.55 %
Refinement TLS params.

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

IDL112)L122)L132)L222)L232)L332)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T112)T122)T132)T222)T232)T332)Origin x (Å)Origin y (Å)Origin z (Å)
12.889-1.3946-0.33814.20760.5562.04990.0082-0.1627-0.0033-0.18690.018-0.2857-0.03720.1834-0.02610.22940.0046-0.0860.158-0.11960.184626.8812-47.336391.3907
24.74410.36052.6224.1663-2.7728.17590.2192-0.4433-0.0810.4926-0.0986-0.37620.7544-0.0051-0.12070.6909-0.0188-0.14150.3772-0.26630.280920.8744-54.0802126.0839
37.26311.3945-4.08072.7206-1.96054.3845-0.3073-0.0938-0.4995-0.11720.0136-0.23630.3119-0.00370.29370.3566-0.0233-0.12180.1833-0.12440.215116.3763-66.3524107.4447
42.35742.081-3.38296.8103-4.87916.9650.1105-0.07370.16890.4573-0.1054-0.0788-0.41410.3878-0.0050.33880.0262-0.08890.1958-0.15820.27526.7447-24.666767.3247
56.39915.14480.84026.03180.43443.36390.07160.29870.8366-0.48710.16920.588-0.3712-0.3489-0.24080.61260.1862-0.04010.5895-0.05620.581223.8536-16.573434.4379
67.7670.17654.22112.8598-0.15456.74360.06950.121-0.40840.019-0.0243-0.0938-0.0151-0.0329-0.04520.0771-0.04220.04110.1453-0.17340.221520.8826-45.594862.6737
78.50144.1108-4.69684.3554-2.43645.6185-0.26760.50160.449-0.25730.40090.54840.1054-0.6628-0.13320.2270.0445-0.14030.3769-0.15270.215523.8201-33.391435.1737
83.0140.96520.65573.03610.59431.81640.0490.0899-0.2386-0.04850.0188-0.10110.32290.1758-0.06780.07450.0601-0.0390.105-0.11480.149828.480921.234744.5745
98.6942-1.7228-4.34271.6025-1.55217.76940.81540.62830.7473-0.486-0.271-0.1408-0.52120.2829-0.54440.7371-0.06520.09510.3522-0.21490.342832.167128.020310.0936
102.6749-0.68613.43182.468-1.18837.1148-0.2380.01920.0619-0.06270.0834-0.0371-0.409-0.39580.15460.12870.0343-0.06840.1672-0.12540.14622.414240.299826.373
111.0748-1.60072.92088.5919-4.15827.95030.020.0778-0.00170.1562-0.0077-0.10990.11840.2026-0.01240.3766-0.0518-0.04920.1912-0.17340.189524.9136-1.286868.2342
124.8659-0.7177-1.08295.058-0.31975.4511-0.3106-0.3112-0.53210.07630.0810.54110.1552-0.27440.22961.2053-0.0627-0.09390.6554-0.1420.784915.1007-10.392399.2167
137.44980.3044-3.24314.2412-1.56656.82550.08820.10280.56220.37580.090.3267-0.2539-0.6629-0.17810.36770.0447-0.12090.1742-0.11050.22615.798618.642271.1447
145.9233-2.54692.39933.9877-1.26583.99730.08660.0222-0.35370.00370.10430.36720.564-0.1606-0.19090.6834-0.0890.0820.5108-0.29070.225412.86246.083998.5686
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A1 - 180
2X-RAY DIFFRACTION1C1 - 10
3X-RAY DIFFRACTION2A181 - 276
4X-RAY DIFFRACTION3B0 - 99
5X-RAY DIFFRACTION4D3 - 110
6X-RAY DIFFRACTION5D115 - 200
7X-RAY DIFFRACTION6E1 - 110
8X-RAY DIFFRACTION7E115 - 241
9X-RAY DIFFRACTION8F1 - 180
10X-RAY DIFFRACTION8H1 - 10
11X-RAY DIFFRACTION9F181 - 276
12X-RAY DIFFRACTION10G0 - 99
13X-RAY DIFFRACTION11I3 - 110
14X-RAY DIFFRACTION12I115 - 200
15X-RAY DIFFRACTION13J1 - 110
16X-RAY DIFFRACTION14J115 - 241

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