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- PDB-2gtz: Human Class I MHC HLA-A2 in complex with the nonameric Melan-A/MA... -

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Basic information

Entry
Database: PDB / ID: 2gtz
TitleHuman Class I MHC HLA-A2 in complex with the nonameric Melan-A/MART-1(27-35) peptide having A28L substitution
Components
  • Beta-2-microglobulinBeta-2 microglobulin
  • HLA-A*0201 heavy chain
  • octapeptide from Melan-A/MART-1Peptide
KeywordsIMMUNE SYSTEM / Melan-A/MART-1 peptide / nonapeptide / MHC class I / HLA-A2 / A28L mutation / melanoma / cancer vaccines
Function / homology
Function and homology information


peptide antigen assembly with MHC class I protein complex / T cell mediated cytotoxicity directed against tumor cell target / antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent / positive regulation of memory T cell activation / TAP complex binding / antigen processing and presentation of exogenous peptide antigen via MHC class I / Golgi medial cisterna / positive regulation of CD8-positive, alpha-beta T cell activation / CD8-positive, alpha-beta T cell activation / positive regulation of CD8-positive, alpha-beta T cell proliferation ...peptide antigen assembly with MHC class I protein complex / T cell mediated cytotoxicity directed against tumor cell target / antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent / positive regulation of memory T cell activation / TAP complex binding / antigen processing and presentation of exogenous peptide antigen via MHC class I / Golgi medial cisterna / positive regulation of CD8-positive, alpha-beta T cell activation / CD8-positive, alpha-beta T cell activation / positive regulation of CD8-positive, alpha-beta T cell proliferation / CD8 receptor binding / endoplasmic reticulum exit site / beta-2-microglobulin binding / TAP binding / protection from natural killer cell mediated cytotoxicity / 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 / detection of bacterium / T cell receptor binding / positive regulation of ferrous iron binding / positive regulation of transferrin receptor binding / early endosome lumen / positive regulation of receptor binding / Nef mediated downregulation of MHC class I complex cell surface expression / DAP12 interactions / negative regulation of receptor binding / lumenal side of endoplasmic reticulum membrane / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent / cellular response to iron(III) ion / negative regulation of forebrain neuron differentiation / trans-Golgi network / ER to Golgi transport vesicle membrane / response to molecule of bacterial origin / regulation of erythrocyte differentiation / regulation of iron ion transport / MHC class I peptide loading complex / HFE-transferrin receptor complex / T cell mediated cytotoxicity / cellular response to iron ion / antigen processing and presentation of endogenous peptide antigen via MHC class I / positive regulation of T cell cytokine production / MHC class I protein complex / multicellular organismal-level iron ion homeostasis / positive regulation of T cell mediated cytotoxicity / peptide antigen assembly with MHC class II protein complex / negative regulation of neurogenesis / positive regulation of receptor-mediated endocytosis / MHC class II protein complex / cellular response to nicotine / recycling endosome membrane / specific granule lumen / phagocytic vesicle membrane / peptide antigen binding / positive regulation of cellular senescence / antigen processing and presentation of exogenous peptide antigen via MHC class II / Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell / Interferon gamma signaling / positive regulation of immune response / melanosome / negative regulation of epithelial cell proliferation / Modulation by Mtb of host immune system / positive regulation of T cell activation / Interferon alpha/beta signaling / positive regulation of type II interferon production / sensory perception of smell / negative regulation of neuron projection development / E3 ubiquitin ligases ubiquitinate target proteins / tertiary granule lumen / DAP12 signaling / MHC class II protein complex binding / late endosome membrane / T cell differentiation in thymus / positive regulation of protein binding / ER-Phagosome pathway / antibacterial humoral response / iron ion transport / T cell receptor signaling pathway / protein refolding / early endosome membrane / protein homotetramerization / intracellular iron ion homeostasis / amyloid fibril formation / learning or memory / defense response to Gram-positive bacterium / immune response / Amyloid fiber formation / lysosomal membrane / endoplasmic reticulum lumen / external side of plasma membrane / Golgi membrane / signaling receptor binding / focal adhesion / innate immune response / Neutrophil degranulation / endoplasmic reticulum membrane / SARS-CoV-2 activates/modulates innate and adaptive immune responses / Golgi apparatus / cell surface
Similarity search - Function
Protein melan-A / Protein melan-A / 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 / Beta-2-Microglobulin / MHC class I-like antigen recognition-like ...Protein melan-A / Protein melan-A / 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 / Beta-2-Microglobulin / MHC class I-like antigen recognition-like / MHC class I-like antigen recognition-like superfamily / MHC classes I/II-like antigen recognition protein / 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
HLA class I histocompatibility antigen, A alpha chain / Beta-2-microglobulin / Melanoma antigen recognized by T-cells 1 / HLA class I histocompatibility antigen, A alpha chain
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.7 Å
AuthorsBorbulevych, O.Y. / Baker, B.M.
CitationJournal: J.Mol.Biol. / Year: 2007
Title: Structures of MART-1(26/27-35) Peptide/HLA-A2 Complexes Reveal a Remarkable Disconnect between Antigen Structural Homology and T Cell Recognition
Authors: Borbulevych, O.Y. / Insaidoo, F.K. / Baxter, T.K. / Powell, D.J. / Johnson, L.A. / Restifo, N.P. / Baker, B.M.
History
DepositionApr 28, 2006Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 12, 2007Provider: repository / Type: Initial release
Revision 1.1May 1, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Advisory / Version format compliance
Revision 1.3Oct 20, 2021Group: Database references / Derived calculations
Category: database_2 / pdbx_struct_conn_angle ...database_2 / pdbx_struct_conn_angle / struct_conn / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.4Aug 30, 2023Group: 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.end_auth_comp_id

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: HLA-A*0201 heavy chain
B: Beta-2-microglobulin
C: octapeptide from Melan-A/MART-1
D: HLA-A*0201 heavy chain
E: Beta-2-microglobulin
F: octapeptide from Melan-A/MART-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)89,77814
Polymers89,1796
Non-polymers5998
Water14,628812
1
A: HLA-A*0201 heavy chain
B: Beta-2-microglobulin
C: octapeptide from Melan-A/MART-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)44,9818
Polymers44,5903
Non-polymers3915
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5350 Å2
ΔGint-34 kcal/mol
Surface area18840 Å2
MethodPISA
2
D: HLA-A*0201 heavy chain
E: Beta-2-microglobulin
F: octapeptide from Melan-A/MART-1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)44,7976
Polymers44,5903
Non-polymers2073
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4700 Å2
ΔGint-32 kcal/mol
Surface area18830 Å2
MethodPISA
Unit cell
Length a, b, c (Å)58.400, 84.310, 84.140
Angle α, β, γ (deg.)90.00, 90.13, 90.00
Int Tables number4
Space group name H-MP1211
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21D
12B
22E

NCS domain segments:

Component-ID: 1 / Refine code: 4

Dom-IDEns-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11ASPASPGLUGLUAA183 - 275183 - 275
21ASPASPGLUGLUDD183 - 275183 - 275
12METMETMETMETBB0 - 991 - 100
22METMETMETMETEE0 - 991 - 100

NCS ensembles :
ID
1
2

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Components

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Protein , 2 types, 4 molecules ADBE

#1: Protein HLA-A*0201 heavy chain / HLA class I histocompatibility antigen / A-2 alpha chain / MHC class I antigen A*2


Mass: 31854.203 Da / Num. of mol.: 2 / Fragment: heavy chain
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HLA-A / Plasmid: pHN1 / Species (production host): Escherichia coli / Production host: Escherichia coli BL21 (bacteria) / Strain (production host): BL21 / References: UniProt: Q9TQH5, UniProt: P04439*PLUS
#2: Protein Beta-2-microglobulin / Beta-2 microglobulin / Beta-2-microglobulin variant pI 5.3


Mass: 11879.356 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: B2M / Plasmid: pHN1 / Species (production host): Escherichia coli / Production host: Escherichia coli BL21 (bacteria) / Strain (production host): BL21 / References: UniProt: P61769

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Protein/peptide , 1 types, 2 molecules CF

#3: Protein/peptide octapeptide from Melan-A/MART-1 / Peptide / Melanoma antigen recognized by T-cells 1


Mass: 856.062 Da / Num. of mol.: 2 / Fragment: residues 27-35 / Mutation: A28L / Source method: obtained synthetically / Details: Commercial synthesis for the peptide / References: UniProt: Q16655

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Non-polymers , 3 types, 820 molecules

#4: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL / Glycerol


Mass: 92.094 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C3H8O3
#5: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Na
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 812 / 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: 2.32 Å3/Da / Density % sol: 47.03 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 6.5
Details: PEG 3350 24%, MES 0.025M, NH4Cl 0.1M, pH 6.5, VAPOR DIFFUSION, SITTING DROP, temperature 277K

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 23-ID-D / Wavelength: 0.979 Å
DetectorType: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Nov 22, 2005
RadiationMonochromator: DOUBLE CRYSTAL SI(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.979 Å / Relative weight: 1
ReflectionResolution: 1.7→20 Å / Num. all: 90210 / Num. obs: 87504 / % possible obs: 97 % / Observed criterion σ(I): 1 / Redundancy: 3.5 % / Biso Wilson estimate: 16.7 Å2 / Rmerge(I) obs: 0.1 / Net I/σ(I): 13.1
Reflection shellResolution: 1.7→1.76 Å / Redundancy: 2.6 % / Rmerge(I) obs: 0.479 / Mean I/σ(I) obs: 2.1 / Num. unique all: 7671 / % possible all: 85.6

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Processing

Software
NameVersionClassification
Blu-Ice(GM/CA)data collection
HKL-2000data reduction
MOLREPphasing
REFMAC5.2refinement
HKL-2000data scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entry 1TVB
Resolution: 1.7→20 Å / Cor.coef. Fo:Fc: 0.961 / Cor.coef. Fo:Fc free: 0.941 / SU B: 4.48 / SU ML: 0.076 / TLS residual ADP flag: LIKELY RESIDUAL / Isotropic thermal model: Isotropic / Cross valid method: THROUGHOUT / σ(F): 1 / ESU R: 0.109 / ESU R Free: 0.112 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.2173 4382 5 %RANDOM
Rwork0.17184 ---
all0.17412 90185 --
obs0.17412 83098 96.95 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 21.719 Å2
Baniso -1Baniso -2Baniso -3
1--0.69 Å20 Å20.17 Å2
2--1.6 Å20 Å2
3----0.91 Å2
Refinement stepCycle: LAST / Resolution: 1.7→20 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6288 0 38 812 7138
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0160.0216574
X-RAY DIFFRACTIONr_angle_refined_deg1.711.9278923
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.1355767
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.73123.152349
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.818151082
X-RAY DIFFRACTIONr_dihedral_angle_4_deg20.8871557
X-RAY DIFFRACTIONr_chiral_restr0.1540.2923
X-RAY DIFFRACTIONr_gen_planes_refined0.0090.025125
X-RAY DIFFRACTIONr_nbd_refined0.1620.082839
X-RAY DIFFRACTIONr_nbtor_refined0.3090.54418
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1890.51138
X-RAY DIFFRACTIONr_metal_ion_refined0.1920.53
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.1240.0872
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.1990.578
X-RAY DIFFRACTIONr_mcbond_it0.9391.53852
X-RAY DIFFRACTIONr_mcangle_it1.70126235
X-RAY DIFFRACTIONr_scbond_it2.88232875
X-RAY DIFFRACTIONr_scangle_it4.6244.52688
Refine LS restraints NCS

Dom-ID: 1 / Refine-ID: X-RAY DIFFRACTION

Ens-IDAuth asym-IDNumberTypeRms dev position (Å)Weight position
1A738medium positional0.240.5
2B839medium positional0.350.5
1A738medium thermal0.82
2B839medium thermal0.822
LS refinement shellResolution: 1.696→1.74 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.298 276 -
Rwork0.223 4966 -
obs--79.14 %
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)
12.0938-0.1446-1.11350.3416-0.18171.7916-0.0401-0.2175-0.08460.0850.0295-0.04530.04420.01970.0106-0.0457-0.0214-0.0291-0.05690.0087-0.060624.082117.293235.4299
21.99350.34261.23580.86290.6353.91280.02050.0698-0.1226-0.04350.0295-0.00610.14430.0305-0.05-0.06990.0063-0.0067-0.12930.0085-0.0803-6.905514.112719.0802
34.1321-0.5426-0.6891.26150.22771.54220.0793-0.0580.35750.0534-0.03610.0609-0.1597-0.0699-0.0432-0.0464-0.00660.0214-0.1185-0.0078-0.0633.270232.152627.1208
41.9143-0.16060.78280.28350.11761.6477-0.0237-0.23270.11320.07170.0080.0576-0.030.0810.0157-0.047-0.01260.0144-0.0419-0.0271-0.04265.1701-17.468220.3141
52.37820.3478-1.66140.9143-0.3993.89690.06550.0560.164-0.06760.00730.0086-0.1302-0.0906-0.0728-0.06410.013-0.0038-0.1061-0.0151-0.077436.1701-14.27283.7881
63.4546-0.52840.24561.4473-0.16621.38120.0066-0.1699-0.2370.026-0.0173-0.04820.09010.14740.0107-0.0697-0.0014-0.0113-0.07270.0101-0.07526.1225-32.270611.9185
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
1X-RAY DIFFRACTION1AA1 - 1821 - 182
2X-RAY DIFFRACTION1CC1 - 91 - 9
3X-RAY DIFFRACTION2AA183 - 275183 - 275
4X-RAY DIFFRACTION3BB0 - 991 - 100
5X-RAY DIFFRACTION4DD1 - 1821 - 182
6X-RAY DIFFRACTION4FF1 - 91 - 9
7X-RAY DIFFRACTION5DD183 - 275183 - 275
8X-RAY DIFFRACTION6EE0 - 991 - 100

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