[English] 日本語
Yorodumi
- PDB-4wdi: Weak TCR binding to an unstable insulin epitope drives type 1 diabetes -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4wdi
TitleWeak TCR binding to an unstable insulin epitope drives type 1 diabetes
Components
  • Beta-2-microglobulin
  • H-2 class I histocompatibility antigen, K-D alpha chain
  • Insulin
KeywordsIMMUNE SYSTEM / Immunoglobulin / H-2Kd / Type 1 Diabetes
Function / homology
Function and homology information


negative regulation of NAD(P)H oxidase activity / negative regulation of glycogen catabolic process / positive regulation of nitric oxide mediated signal transduction / negative regulation of fatty acid metabolic process / negative regulation of feeding behavior / Signaling by Insulin receptor / IRS activation / Insulin processing / regulation of protein secretion / positive regulation of peptide hormone secretion ...negative regulation of NAD(P)H oxidase activity / negative regulation of glycogen catabolic process / positive regulation of nitric oxide mediated signal transduction / negative regulation of fatty acid metabolic process / negative regulation of feeding behavior / Signaling by Insulin receptor / IRS activation / Insulin processing / regulation of protein secretion / positive regulation of peptide hormone secretion / positive regulation of respiratory burst / antigen processing and presentation of exogenous peptide antigen via MHC class I / negative regulation of acute inflammatory response / Regulation of gene expression in beta cells / inner ear development / alpha-beta T cell activation / regulation of amino acid metabolic process / 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 / negative regulation of protein secretion / positive regulation of dendritic spine maintenance / positive regulation of glycogen biosynthetic process / Synthesis, secretion, and deacylation of Ghrelin / regulation of protein localization to plasma membrane / fatty acid homeostasis / beta-2-microglobulin binding / negative regulation of gluconeogenesis / negative regulation of lipid catabolic process / Signal attenuation / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / COPI-mediated anterograde transport / positive regulation of lipid biosynthetic process / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / positive regulation of insulin receptor signaling pathway / nitric oxide-cGMP-mediated signaling / negative regulation of reactive oxygen species biosynthetic process / positive regulation of protein autophosphorylation / Insulin receptor recycling / transport vesicle / insulin-like growth factor receptor binding / neuron projection maintenance / endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of brown fat cell differentiation / positive regulation of protein metabolic process / NPAS4 regulates expression of target genes / activation of protein kinase B activity / positive regulation of glycolytic process / Insulin receptor signalling cascade / positive regulation of mitotic nuclear division / positive regulation of ferrous iron binding / positive regulation of transferrin receptor binding / positive regulation of nitric-oxide synthase activity / positive regulation of receptor binding / early endosome lumen / Nef mediated downregulation of MHC class I complex cell surface expression / negative regulation of receptor binding / DAP12 interactions / antigen processing and presentation of endogenous peptide antigen via MHC class Ib / antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent / positive regulation of cytokine production / positive regulation of long-term synaptic potentiation / acute-phase response / endosome lumen / Regulation of insulin secretion / positive regulation of D-glucose import / positive regulation of protein secretion / cellular response to iron ion / negative regulation of proteolysis / Endosomal/Vacuolar pathway / positive regulation of cell differentiation / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / lumenal side of endoplasmic reticulum membrane / regulation of transmembrane transporter activity / insulin receptor binding / peptide 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 / regulation of erythrocyte differentiation / peptide antigen assembly with MHC class I protein complex / ER to Golgi transport vesicle membrane / regulation of iron ion transport / response to molecule of bacterial origin / MHC class I peptide loading complex / HFE-transferrin receptor complex / regulation of synaptic plasticity / negative regulation of protein catabolic process / T cell mediated cytotoxicity / hormone activity / positive regulation of T cell cytokine production / antigen processing and presentation of endogenous peptide antigen via MHC class I / MHC class I protein complex / positive regulation of neuron projection development / negative regulation of neurogenesis / cognition / positive regulation of receptor-mediated endocytosis / positive regulation of protein localization to nucleus / peptide antigen assembly with MHC class II protein complex / multicellular organismal-level iron ion homeostasis
Similarity search - Function
Insulin / Insulin family / Insulin-like / Insulin/IGF/Relaxin family / Insulin / insulin-like growth factor / relaxin family. / Insulin, conserved site / Insulin family signature. / Insulin-like superfamily / MHC class I-like antigen recognition-like / Murine Class I Major Histocompatibility Complex, H2-DB; Chain A, domain 1 ...Insulin / Insulin family / Insulin-like / Insulin/IGF/Relaxin family / Insulin / insulin-like growth factor / relaxin family. / Insulin, conserved site / Insulin family signature. / Insulin-like superfamily / 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
Insulin / H-2 class I histocompatibility antigen, K-D alpha chain / Beta-2-microglobulin
Similarity search - Component
Biological speciesMus musculus (house mouse)
Homo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.313 Å
Model detailsG9G in H-2Kd, Triclinic form
AuthorsRizkallah, P.J. / Cole, D.K.
CitationJournal: J.Biol.Chem. / Year: 2015
Title: Distortion of the Major Histocompatibility Complex Class I Binding Groove to Accommodate an Insulin-derived 10-Mer Peptide.
Authors: Motozono, C. / Pearson, J.A. / De Leenheer, E. / Rizkallah, P.J. / Beck, K. / Trimby, A. / Sewell, A.K. / Wong, F.S. / Cole, D.K.
History
DepositionSep 8, 2014Deposition site: RCSB / Processing site: PDBE
Revision 1.0Jun 24, 2015Provider: repository / Type: Initial release
Revision 1.1Jul 1, 2015Group: Database references
Revision 1.2Oct 16, 2024Group: Data collection / Database references / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / diffrn_radiation_wavelength / pdbx_entry_details / pdbx_modification_feature
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: H-2 class I histocompatibility antigen, K-D alpha chain
B: Beta-2-microglobulin
C: Insulin
D: H-2 class I histocompatibility antigen, K-D alpha chain
E: Beta-2-microglobulin
F: Insulin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)90,93111
Polymers90,4856
Non-polymers4465
Water2,882160
1
A: H-2 class I histocompatibility antigen, K-D alpha chain
B: Beta-2-microglobulin
C: Insulin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)45,5937
Polymers45,2433
Non-polymers3504
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5330 Å2
ΔGint-70 kcal/mol
Surface area18860 Å2
MethodPISA
2
D: H-2 class I histocompatibility antigen, K-D alpha chain
E: Beta-2-microglobulin
F: Insulin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)45,3394
Polymers45,2433
Non-polymers961
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4780 Å2
ΔGint-41 kcal/mol
Surface area18770 Å2
MethodPISA
Unit cell
Length a, b, c (Å)46.930, 62.690, 72.670
Angle α, β, γ (deg.)68.110, 85.790, 85.180
Int Tables number1
Space group name H-MP1
DetailsChains A, B and C form one biological entity. / Chains D,E,F form one biological entity.

-
Components

-
Protein , 2 types, 4 molecules ADBE

#1: Protein H-2 class I histocompatibility antigen, K-D alpha chain / H-2K(D)


Mass: 32353.016 Da / Num. of mol.: 2 / Fragment: H-2Kd MHC, residues 22-296
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: H2-K1, H2-K / Plasmid: pGMT7 / Production host: Escherichia coli (E. coli) / Variant (production host): rosetta / References: UniProt: P01902*PLUS
#2: Protein Beta-2-microglobulin


Mass: 11879.356 Da / Num. of mol.: 2 / Fragment: Human beta2-microglobulin, residues 21-219
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: B2M, CDABP0092, HDCMA22P / Plasmid: pGMT7 / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): rosetta / References: UniProt: P61769

-
Protein/peptide , 1 types, 2 molecules CF

#3: Protein/peptide Insulin


Mass: 1010.190 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: INS / Production host: synthetic construct (others) / References: UniProt: P01308

-
Non-polymers , 3 types, 165 molecules

#4: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6O2
#5: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: SO4
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 160 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.18 Å3/Da / Density % sol: 43.64 %
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop / pH: 8
Details: 20% PEG 3350, 0.2 M Sodium malonate, and 0.1 M Bis-Tris Propane, pH 6.5

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04-1 / Wavelength: 0.917 Å
DetectorType: DECTRIS PILATUS 2M / Detector: PIXEL / Date: Feb 9, 2012 / Details: mirrors
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.917 Å / Relative weight: 1
ReflectionResolution: 2.313→29.518 Å / Num. all: 30132 / Num. obs: 30132 / % possible obs: 90.2 % / Redundancy: 2.1 % / Rpim(I) all: 0.081 / Rrim(I) all: 0.12 / Rsym value: 0.068 / Net I/av σ(I): 10 / Net I/σ(I): 8.6 / Num. measured all: 64672
Reflection shell

Diffraction-ID: 1 / Rejects: _

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured allNum. unique allRpim(I) allRsym valueNet I/σ(I) obs% possible all
2.31-2.372.20.3512.2491622610.430.351291.5
2.37-2.442.20.3272.3473321890.3910.3272.290.9
2.44-2.512.20.2682.8458021130.3330.2682.589.5
2.51-2.592.20.2632.9446720420.3060.2632.989.8
2.59-2.672.10.1914409519200.240.1913.488.2
2.67-2.762.10.1694.6396018710.2130.1693.986.8
2.76-2.872.10.1256.1330815990.1680.1254.877.6
2.87-2.992.10.1077355416780.1360.107684.6
2.99-3.122.20.0968.2392618200.1150.0967.395
3.12-3.272.10.0769.9365917020.0960.076994.8
3.27-3.452.20.05912.4355316440.080.05910.894.8
3.45-3.662.20.0514.6329515260.0640.0513.194.3
3.66-3.912.20.04714.8317514640.0650.04714.793.7
3.91-4.222.10.03715.9279113200.0530.03716.793
4.22-4.632.10.03718.8250111850.0480.03718.791.1
4.63-5.172.10.03220.5223510510.0490.03219.387.2
5.17-5.972.10.03616.517508400.0470.03618.380.3
5.97-7.322.20.03918.119038670.0460.03917.999.5
7.32-10.352.20.0341915016870.0340.0342299.6
10.35-29.5182.20.029247703530.0290.02923.595

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassification
REFMAC5.5.0109refinement
PDB_EXTRACT3.15data extraction
SCALAdata scaling
PHASERphasing
GDAdata collection
GDAdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.313→29.518 Å / Cor.coef. Fo:Fc: 0.941 / Cor.coef. Fo:Fc free: 0.895 / WRfactor Rfree: 0.2791 / WRfactor Rwork: 0.2004 / FOM work R set: 0.8015 / SU B: 19.774 / SU ML: 0.235 / SU R Cruickshank DPI: 0.861 / SU Rfree: 0.3211 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.861 / ESU R Free: 0.321 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.2834 1527 5.1 %RANDOM
Rwork0.2061 28604 --
obs0.21 30131 100 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso max: 100.76 Å2 / Biso mean: 32.807 Å2 / Biso min: 11.48 Å2
Baniso -1Baniso -2Baniso -3
1-1.01 Å2-0.54 Å2-0.1 Å2
2--0.25 Å21.46 Å2
3----2.24 Å2
Refinement stepCycle: final / Resolution: 2.313→29.518 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6388 0 24 160 6572
Biso mean--57.81 32.46 -
Num. residues----772
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0160.0216658
X-RAY DIFFRACTIONr_bond_other_d0.0010.024585
X-RAY DIFFRACTIONr_angle_refined_deg1.5981.9389055
X-RAY DIFFRACTIONr_angle_other_deg0.89311016
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.395778
X-RAY DIFFRACTIONr_dihedral_angle_2_deg31.71823.204362
X-RAY DIFFRACTIONr_dihedral_angle_3_deg18.666151073
X-RAY DIFFRACTIONr_dihedral_angle_4_deg19.9931560
X-RAY DIFFRACTIONr_chiral_restr0.0940.2910
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.0217494
X-RAY DIFFRACTIONr_gen_planes_other0.0010.021492
X-RAY DIFFRACTIONr_mcbond_it0.61.53886
X-RAY DIFFRACTIONr_mcbond_other0.1351.51560
X-RAY DIFFRACTIONr_mcangle_it1.08626276
X-RAY DIFFRACTIONr_scbond_it1.7532772
X-RAY DIFFRACTIONr_scangle_it2.6374.52779
LS refinement shellResolution: 2.313→2.373 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.326 115 -
Rwork0.277 2131 -
all-2246 -
obs--100 %
Refinement TLS params.

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

IDL11 (°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)
11.68720.55371.52951.47840.00075.4494-0.1798-0.10190.44820.2549-0.0941-0.1711-1.29720.29080.27390.4029-0.0895-0.07180.13160.00620.241548.345653.895135.9216
23.12061.2555-1.58226.9749-3.48372.6819-0.15630.1535-0.3574-0.12950.0645-0.12350.24420.11890.09180.03810.033-0.00130.1028-0.02040.066552.48925.511859.9691
32.2294-0.1679-0.84080.7955-1.51716.353-0.0022-0.0110.06190.20660.02750.179-0.5065-0.4489-0.02540.09040.03530.03150.0683-0.03750.114336.442441.371957.0621
41.3909-0.8398-1.32061.15660.85494.9306-0.0872-0.1003-0.2936-0.0007-0.00050.03750.96710.07120.08770.2895-0.02080.02340.1110.04380.128624.964820.486731.9221
53.471-1.76051.9456.4273-4.02844.3183-0.1216-0.00560.4850.0162-0.041-0.1267-0.32880.10040.16270.0573-0.0173-0.01010.0459-0.00270.071628.919848.84157.8514
62.326-0.1320.20371.3964-2.0857.41630.15250.0053-0.0552-0.2376-0.05070.30090.4213-0.5414-0.10180.0547-0.0095-0.04920.1106-0.04630.109112.878632.87410.825
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A0 - 180
2X-RAY DIFFRACTION1C1 - 9
3X-RAY DIFFRACTION2A181 - 276
4X-RAY DIFFRACTION3B0 - 99
5X-RAY DIFFRACTION4D0 - 180
6X-RAY DIFFRACTION4F1 - 9
7X-RAY DIFFRACTION5D181 - 276
8X-RAY DIFFRACTION6E0 - 99

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more