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- PDB-4l3e: The complex between high affinity TCR DMF5(alpha-D26Y,beta-L98W) ... -

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Basic information

Entry
Database: PDB / ID: 4l3e
TitleThe complex between high affinity TCR DMF5(alpha-D26Y,beta-L98W) and human Class I MHC HLA-A2 with the bound MART-1(26-35)(A27L) peptide
Components
  • Beta-2-microglobulinBeta-2 microglobulin
  • DMF5 alpha chain
  • DMF5 beta chain
  • HLA class I histocompatibility antigen, A-2 alpha chain
  • Melanoma antigen recognized by T-cells 1
KeywordsIMMUNE SYSTEM / receptors / membrane
Function / homology
Function and homology information


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 ...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 / peptide antigen assembly with MHC class I protein complex / 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 / MHC class II protein complex / positive regulation of receptor-mediated endocytosis / cellular response to nicotine / recycling endosome membrane / phagocytic vesicle membrane / specific granule lumen / 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 / structural molecule activity / Golgi apparatus
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 / HLA class I histocompatibility antigen, A alpha chain / Beta-2-microglobulin / Melanoma antigen recognized by T-cells 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.557 Å
AuthorsHellman, L.M.
CitationJournal: PLOS COMPUT.BIOL. / Year: 2014
Title: Computational design of the affinity and specificity of a therapeutic T cell receptor.
Authors: Pierce, B.G. / Hellman, L.M. / Hossain, M. / Singh, N.K. / Vander Kooi, C.W. / Weng, Z. / Baker, B.M.
History
DepositionJun 5, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 11, 2014Provider: repository / Type: Initial release
Revision 1.1Aug 27, 2014Group: Database references

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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: Melanoma antigen recognized by T-cells 1
D: DMF5 alpha chain
E: DMF5 beta chain


Theoretical massNumber of molelcules
Total (without water)93,7755
Polymers93,7755
Non-polymers00
Water21612
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area11050 Å2
ΔGint-56 kcal/mol
Surface area37090 Å2
MethodPISA
Unit cell
Length a, b, c (Å)227.040, 49.316, 92.894
Angle α, β, γ (deg.)90.00, 94.82, 90.00
Int Tables number5
Space group name H-MC121

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Components

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Protein , 4 types, 4 molecules ABDE

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


Mass: 31854.203 Da / Num. of mol.: 1 / Fragment: UNP residues 25-299
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 / Beta-2 microglobulin


Mass: 11879.356 Da / Num. of mol.: 1 / Fragment: UNP residues 21-119
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
#4: Protein DMF5 alpha chain


Mass: 22055.312 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TRAC, TCRA / Production host: Escherichia coli (E. coli)
#5: Protein DMF5 beta chain


Mass: 27001.045 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli)

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Protein/peptide / Non-polymers , 2 types, 13 molecules C

#3: Protein/peptide Melanoma antigen recognized by T-cells 1 / MART-1 / Antigen LB39-AA / Antigen SK29-AA / Protein Melan-A


Mass: 985.176 Da / Num. of mol.: 1 / Fragment: UNP residues 26-35 / Mutation: A27L / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: Q16655
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 12 / 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: 2.76 Å3/Da / Density % sol: 55.48 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 8
Details: 12% PEG3350, 0.1 M Tris-HCl, 0.25 M magnesium chloride, pH 8, VAPOR DIFFUSION, HANGING DROP, temperature 298K

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Data collection

DiffractionMean temperature: 298 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-ID / Wavelength: 1 Å
DetectorType: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Nov 26, 2012
RadiationMonochromator: Rosenbaum-Rock double-crystal Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.5568→20.047 Å / Num. all: 31904 / Num. obs: 31904 / % possible obs: 94.82 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2 / Redundancy: 3.8 % / Rmerge(I) obs: 0.088 / Net I/σ(I): 11.74
Reflection shellResolution: 2.5568→2.64 Å / Redundancy: 2.9 % / Rmerge(I) obs: 0.438 / Mean I/σ(I) obs: 2 / % possible all: 83.3

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Processing

Software
NameVersionClassification
HKL-2000data collection
PHENIXmodel building
PHENIX(phenix.refine: 1.8.2_1309)refinement
HKL-2000data reduction
HKL-2000data scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.557→20.047 Å / SU ML: 0.38 / σ(F): 1.35 / Phase error: 35.62 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2663 1625 5.11 %
Rwork0.2289 --
obs0.2309 31816 94.56 %
all-31815 -
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.557→20.047 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6603 0 0 12 6615
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0096782
X-RAY DIFFRACTIONf_angle_d1.1519198
X-RAY DIFFRACTIONf_dihedral_angle_d16.5912453
X-RAY DIFFRACTIONf_chiral_restr0.075966
X-RAY DIFFRACTIONf_plane_restr0.0051206
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.557-2.63190.42641110.37552087X-RAY DIFFRACTION80
2.6319-2.71660.33741060.35422277X-RAY DIFFRACTION86
2.7166-2.81350.46411280.34842340X-RAY DIFFRACTION89
2.8135-2.92580.37361350.33112466X-RAY DIFFRACTION93
2.9258-3.05850.30661420.28682516X-RAY DIFFRACTION96
3.0585-3.21910.39561190.30472613X-RAY DIFFRACTION98
3.2191-3.41990.33861350.2682603X-RAY DIFFRACTION98
3.4199-3.68240.28781480.24162616X-RAY DIFFRACTION99
3.6824-4.05020.23381430.22362644X-RAY DIFFRACTION99
4.0502-4.630.24451530.19022619X-RAY DIFFRACTION99
4.63-5.80970.21951550.18572667X-RAY DIFFRACTION99
5.8097-20.04730.21791500.18522743X-RAY DIFFRACTION99
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)
11.1255-0.56130.21930.96020.06721.5430.17680.3791-0.1218-0.0594-0.15010.22620.59110.30510.06150.24060.190.0685-0.0216-0.12190.2766-41.0144-22.39-6.0475
21.0297-0.31640.51251.30330.54211.64140.09530.2670.2738-0.2068-0.1415-0.1018-0.37410.40310.16730.2154-0.08850.10880.07870.0420.6339-38.9297-7.2728-2.5562
31.6813-0.49850.89971.1715-0.55240.97160.2610.68710.3008-0.242-0.0754-0.3374-0.02580.6029-0.2650.1931-0.02010.08760.3670.01590.4378-30.9482-12.632-8.5695
41.2468-0.78150.83861.15290.03281.0503-0.13170.38030.8579-0.35510.11280.2923-0.8137-0.13380.12530.7760.12620.04080.72340.53040.8633-53.8529-1.8446-31.4016
50.0639-0.1209-0.12090.24340.2430.2428-0.13230.48080.4662-0.41810.01770.0969-0.7425-0.1151-0.03361.03740.09130.05720.88520.64651.1143-55.83354.4773-36.0393
61.3105-0.2269-0.31922.4567-0.04921.21360.04250.37240.3842-0.4109-0.04590.1111-0.4777-0.1112-0.0120.8161-0.06310.1520.97920.53461.088-45.4108-1.4982-39.3532
79.54793.38285.68898.53346.92529.7306-0.3016-0.14240.35120.1024-0.0129-0.9298-0.53460.61690.30330.25010.0234-0.11880.21350.09360.6466-58.4355-6.5435-4.9737
83.21290.12710.27523.4921.4483.87480.04430.7956-0.035-0.7967-0.0110.04340.35450.1329-0.06480.53670.1355-0.08510.32950.14240.275-58.0644-17.3793-30.3657
90.1720.16750.01040.32520.2920.56610.14350.1281-0.082-0.1586-0.01450.07140.20280.05140.00060.2590.166-0.01290.08170.12740.3105-59.2358-17.899-17.2638
103.79330.16632.47381.4735-0.02023.25110.2145-0.0466-0.4498-0.03120.02750.0280.4725-0.0547-0.20020.36240.046-0.10130.1992-0.04410.187-64.0235-26.9674-19.9566
112.1463-0.01881.91072.59390.80343.77260.06540.1296-0.1312-0.34390.0999-0.06730.06340.09070.0190.27150.01390.07030.01650.05960.3237-52.1513-16.5755-15.7364
122.56730.03192.99452.7844-1.27544.12190.19040.81010.0469-1.0580.00260.7159-0.1237-0.5971-0.20720.80040.0115-0.31470.54390.02020.6618-69.3626-22.3871-34.215
130.41040.12170.53130.86030.43821.39220.06560.0298-0.1-0.0895-0.05940.031-0.0864-0.0310.01270.25880.0849-0.05850.0440.05840.4153-66.9549-14.8389-13.2856
143.6796-1.69640.97334.31751.08314.73380.12810.57360.4048-0.7165-0.2791-0.2877-0.380.27080.16490.45730.177-0.0560.3430.22230.4609-65.7078-12.6303-27.7693
151.40540.15470.54290.7727-0.46180.70550.23590.1653-0.0262-0.0372-0.09120.1485-0.03980.1363-0.06590.1392-0.00260.09970.1058-0.0440.214-33.1214-16.82931.1018
165.3450.67512.22221.09230.08350.96340.39180.5443-0.8032-0.3621-0.1826-0.09060.0863-0.1065-0.33110.52130.3257-0.03881.1986-0.30070.532-7.1821-32.10033.3384
170.3315-0.02-0.01070.0065-0.04190.21980.14830.21780.0354-0.01220.0181-0.16360.03860.3044-0.04550.24490.30520.12771.0262-0.18470.4282-12.0535-24.5308-0.6541
180.8346-0.2922-0.14890.3030.09530.18490.12830.02460.38880.06690.0472-0.27-0.00020.1272-0.09250.10390.23610.13850.9785-0.15870.3286-12.5996-19.46577.0976
190.6018-0.1002-0.29260.3274-0.08750.56910.0996-0.00610.25670.0236-0.0907-0.2059-0.01580.4818-0.14240.23360.21170.02881.1009-0.15840.3544-10.8094-23.42194.6006
204.4048-1.03681.43422.0722-0.71840.54640.2097-0.3375-0.11370.1052-0.2958-0.76160.01860.65950.06240.32030.15320.05231.26910.00060.52111.8011-28.903313.3694
215.91280.48561.06671.85851.2730.9650.1646-0.9184-0.54140.4484-0.10390.02070.31130.330.01060.74320.21270.00391.76430.21560.958510.7525-43.952737.7905
221.8384-1.4910.76611.9651-2.14889.0446-0.0723-0.1312-0.1826-0.2268-0.0215-0.0667-0.21970.39090.06910.49410.1540.00821.6255-0.07730.611413.4175-36.156222.684
231.3360.82271.30046.22570.92431.2676-0.1298-0.0341-0.2718-0.42890.55030.77390.3829-0.471-0.39140.7058-0.04520.06271.3299-0.00620.88957.6913-48.030619.4869
241.907-0.1128-0.330.5876-1.31083.1084-0.172-0.03190.0733-0.3087-0.0926-0.1578-0.04990.32040.19330.5502-0.0349-0.05081.53560.10730.67686.84-31.440125.4267
252.2644-1.1038-0.12210.93110.46031.69710.1132-0.28-0.8746-0.0773-0.0587-0.55990.32450.3442-0.05240.68510.2294-0.16291.76810.12940.902510.6661-43.737128.2357
260.82681.18611.7231.81092.46933.59080.1350.0526-0.174-0.38880.0646-0.0492-0.00340.3207-0.15310.58840.0940.0811.7718-0.10440.859519.36-42.499821.9785
271.3759-0.52950.160.91260.36491.23880.3593-0.0273-0.58310.05260.0825-0.06260.61930.4416-0.03340.40470.1821-0.140.094-0.29610.3579-27.6378-32.734217.0485
282.7960.5145-0.00262.5827-0.76281.1270.0938-0.0127-0.43640.0149-0.02-0.21490.01430.9106-0.12950.58160.08-0.14911.1904-0.00380.493-0.2434-37.536233.8021
293.87961.21161.26315.04620.11473.2790.1062-0.3412-0.47690.45710.21940.7014-0.013-0.0944-0.38360.54580.0557-0.08880.91660.13010.4554-12.3687-42.926440.5451
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 1 through 84 )
2X-RAY DIFFRACTION2chain 'A' and (resid 85 through 137 )
3X-RAY DIFFRACTION3chain 'A' and (resid 138 through 185 )
4X-RAY DIFFRACTION4chain 'A' and (resid 186 through 242 )
5X-RAY DIFFRACTION5chain 'A' and (resid 243 through 262 )
6X-RAY DIFFRACTION6chain 'A' and (resid 263 through 275 )
7X-RAY DIFFRACTION7chain 'B' and (resid 0 through 5 )
8X-RAY DIFFRACTION8chain 'B' and (resid 6 through 19 )
9X-RAY DIFFRACTION9chain 'B' and (resid 20 through 41 )
10X-RAY DIFFRACTION10chain 'B' and (resid 42 through 51 )
11X-RAY DIFFRACTION11chain 'B' and (resid 52 through 71 )
12X-RAY DIFFRACTION12chain 'B' and (resid 72 through 77 )
13X-RAY DIFFRACTION13chain 'B' and (resid 78 through 90 )
14X-RAY DIFFRACTION14chain 'B' and (resid 91 through 99 )
15X-RAY DIFFRACTION15chain 'C' and (resid 1 through 10 )
16X-RAY DIFFRACTION16chain 'D' and (resid 1 through 13 )
17X-RAY DIFFRACTION17chain 'D' and (resid 14 through 31 )
18X-RAY DIFFRACTION18chain 'D' and (resid 32 through 65 )
19X-RAY DIFFRACTION19chain 'D' and (resid 66 through 96 )
20X-RAY DIFFRACTION20chain 'D' and (resid 97 through 116 )
21X-RAY DIFFRACTION21chain 'D' and (resid 117 through 130 )
22X-RAY DIFFRACTION22chain 'D' and (resid 131 through 140 )
23X-RAY DIFFRACTION23chain 'D' and (resid 141 through 150 )
24X-RAY DIFFRACTION24chain 'D' and (resid 151 through 165 )
25X-RAY DIFFRACTION25chain 'D' and (resid 166 through 184 )
26X-RAY DIFFRACTION26chain 'D' and (resid 185 through 199 )
27X-RAY DIFFRACTION27chain 'E' and (resid 4 through 115 )
28X-RAY DIFFRACTION28chain 'E' and (resid 116 through 215 )
29X-RAY DIFFRACTION29chain 'E' and (resid 216 through 245 )

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