[English] 日本語
Yorodumi
- PDB-4z76: Weak TCR binding to an unstable insulin epitope drives type 1 diabetes -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4z76
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 / positive regulation of dendritic spine maintenance / 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 / beta-2-microglobulin binding / negative regulation of lipid catabolic process / negative regulation of gluconeogenesis / 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 / transport vesicle / positive regulation of protein autophosphorylation / Insulin receptor recycling / insulin-like growth factor receptor binding / neuron projection maintenance / positive regulation of protein metabolic process / NPAS4 regulates expression of target genes / positive regulation of brown fat cell differentiation / activation of protein kinase B activity / endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of glycolytic process / 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 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 / positive regulation of D-glucose import / negative regulation of proteolysis / positive regulation of protein secretion / cellular response to iron ion / Regulation of insulin secretion / positive regulation of cell differentiation / Endosomal/Vacuolar pathway / Antigen Presentation: Folding, assembly and peptide loading of class I MHC / lumenal side of endoplasmic reticulum membrane / insulin receptor binding / regulation of transmembrane transporter activity / 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 / negative regulation of protein catabolic process / regulation of synaptic plasticity / hormone activity / T cell mediated cytotoxicity / antigen processing and presentation of endogenous peptide antigen via MHC class I / positive regulation of T cell cytokine production / MHC class I protein complex / positive regulation of neuron projection development / negative regulation of neurogenesis / cognition / positive regulation of receptor-mediated endocytosis / peptide antigen assembly with MHC class II protein complex / positive regulation of protein localization to nucleus / 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 / Resolution: 1.88 Å
Model detailsG9V 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
DepositionApr 6, 2015Deposition site: RCSB / Processing site: PDBE
Revision 1.0Jun 24, 2015Provider: repository / Type: Initial release
Revision 1.1Jul 1, 2015Group: Database references
Revision 1.2Aug 12, 2015Group: Database references
Revision 1.3Oct 23, 2024Group: Data collection / Database references ...Data collection / Database references / Refinement description / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature / 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

-
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)92,65930
Polymers90,5696
Non-polymers2,09024
Water8,377465
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)46,16314
Polymers45,2853
Non-polymers87911
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area6980 Å2
ΔGint-92 kcal/mol
Surface area18830 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)46,49516
Polymers45,2853
Non-polymers1,21113
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area6640 Å2
ΔGint-161 kcal/mol
Surface area19190 Å2
MethodPISA
Unit cell
Length a, b, c (Å)47.990, 62.370, 72.310
Angle α, β, γ (deg.)69.810, 85.760, 87.050
Int Tables number1
Space group name H-MP1
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21D
12B
22E

NCS domain segments:

Component-ID: _ / Beg auth comp-ID: MET / Beg label comp-ID: MET / Refine code: _

Dom-IDEns-IDEnd auth comp-IDEnd label comp-IDAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11PROPROAA0 - 2761 - 277
21PROPRODD0 - 2761 - 277
12METMETBB0 - 991 - 100
22METMETEE0 - 991 - 100

NCS ensembles :
ID
1
2

-
Components

-
Protein , 2 types, 4 molecules ADBE

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


Mass: 32353.016 Da / Num. of mol.: 2 / Fragment: UNP 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 BL21(DE3) (bacteria) / Variant (production host): rosetta / References: UniProt: P01902
#2: Protein Beta-2-microglobulin


Mass: 11879.356 Da / Num. of mol.: 2 / Fragment: UNP residues 21-119
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: 1052.269 Da / Num. of mol.: 2 / Fragment: UNP residues 39-47
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 , 4 types, 489 molecules

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


Mass: 62.068 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C2H6O2
#5: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C3H8O3
#6: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 15 / Source method: obtained synthetically / Formula: SO4
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 465 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION

-
Sample preparation

CrystalDensity Matthews: 2.24 Å3/Da / Density % sol: 44.99 %
Crystal growTemperature: 291 K / Method: vapor diffusion / pH: 8
Details: G9V crystals were grown in 20% PEG 6000, 0.2 M calcium chloride, 0.1 M Tris propane pH 8.0

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04-1 / Wavelength: 0.9173 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Feb 9, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9173 Å / Relative weight: 1
ReflectionResolution: 1.88→38.268 Å / Num. all: 57349 / Num. obs: 57349 / % possible obs: 89.9 % / Redundancy: 2.1 % / Rpim(I) all: 0.099 / Rrim(I) all: 0.144 / Rsym value: 0.057 / Net I/av σ(I): 10.684 / Net I/σ(I): 8.6 / Num. measured all: 122779
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
1.88-1.932.20.2722.6926342450.6430.272289.9
1.93-1.982.10.2113.4865040320.5050.2112.587.8
1.98-2.042.10.1734.1825938720.4260.173386.3
2.04-2.12.10.1594.6770336520.3570.1593.583.7
2.1-2.172.10.1355.3653231220.2940.1354.274.3
2.17-2.252.10.1037.1798437540.2530.1034.792.2
2.25-2.332.20.0977.6806337420.2170.0975.494.7
2.33-2.432.20.0829.2770435710.1870.0826.194.7
2.43-2.542.10.0789.2740734460.1740.0786.594.6
2.54-2.662.10.06711.1699532590.1380.0677.894.1
2.66-2.82.20.05513.1675130980.1190.0559.193.8
2.8-2.972.10.04616.1619829190.1030.04610.593.2
2.97-3.182.10.0417.9567026720.080.0412.591.7
3.18-3.432.10.03718518624600.0670.03714.690
3.43-3.762.10.03320.3462021710.0550.03317.686.9
3.76-4.22.10.02722.1356916940.0480.02720.374.8
4.2-4.852.20.0319.6431019890.0460.0322.298.6
4.85-5.952.20.02726.1365716770.0480.02722.199.2
5.95-8.412.20.03319.3274412720.0560.0332198.9
8.41-38.2682.20.03318.715147020.0480.03325.697.7

-
Processing

Software
NameVersionClassification
REFMAC5.8.0073refinement
xia2data reduction
SCALAdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.88→38.268 Å / Cor.coef. Fo:Fc: 0.957 / Cor.coef. Fo:Fc free: 0.933 / WRfactor Rfree: 0.2169 / WRfactor Rwork: 0.1721 / FOM work R set: 0.8159 / SU B: 9.281 / SU ML: 0.134 / SU R Cruickshank DPI: 0.1906 / SU Rfree: 0.1647 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.191 / ESU R Free: 0.165 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.2296 2886 5.1 %RANDOM
Rwork0.184 ---
obs0.1863 54089 89.27 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 107.86 Å2 / Biso mean: 27.817 Å2 / Biso min: 9.32 Å2
Baniso -1Baniso -2Baniso -3
1--0.2 Å2-0.59 Å20.54 Å2
2--1.73 Å20.15 Å2
3----1.12 Å2
Refinement stepCycle: final / Resolution: 1.88→38.268 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6394 0 117 465 6976
Biso mean--56.52 33.87 -
Num. residues----772
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0150.0196758
X-RAY DIFFRACTIONr_bond_other_d0.0050.026090
X-RAY DIFFRACTIONr_angle_refined_deg1.7731.9469180
X-RAY DIFFRACTIONr_angle_other_deg1.187313983
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.7325781
X-RAY DIFFRACTIONr_dihedral_angle_2_deg30.97623360
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.252151081
X-RAY DIFFRACTIONr_dihedral_angle_4_deg21.3361563
X-RAY DIFFRACTIONr_chiral_restr0.1110.2938
X-RAY DIFFRACTIONr_gen_planes_refined0.0090.0217612
X-RAY DIFFRACTIONr_gen_planes_other0.0040.021699
X-RAY DIFFRACTIONr_mcbond_it1.2211.3883121
X-RAY DIFFRACTIONr_mcbond_other1.2211.3883120
X-RAY DIFFRACTIONr_mcangle_it2.0382.0713903
Refine LS restraints NCS

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

Ens-IDDom-IDAuth asym-IDNumberRms dev position (Å)
11A154210.13
12D154210.13
21B56500.11
22E56500.11
LS refinement shellResolution: 1.88→1.929 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.309 187 -
Rwork0.28 3808 -
all-3995 -
obs--84.8 %
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)
11.3570.11630.88710.93540.24072.5605-0.04670.0050.22140.00420.0193-0.0261-0.24840.09790.02740.0333-0.02560.01320.0403-0.0350.109548.6953.356336.2979
22.35580.7827-0.9353.6845-1.97732.7534-0.1155-0.1505-0.3652-0.1262-0.0019-0.20290.46990.1330.11740.10770.03330.01030.0758-0.0240.103253.208824.412960.0116
31.71740.0494-0.19440.859-0.20953.7002-0.0185-0.09880.0350.10470.11030.1132-0.0544-0.1426-0.09180.01340.01490.01550.0587-0.03160.080536.365240.36757.1293
41.323-0.3509-0.67681.03860.33143.0552-0.02370.0551-0.1538-0.00370.02450.02080.29310.1013-0.00080.03030.0115-0.00490.0319-0.04870.085224.800820.374632.0997
52.6444-0.08760.57392.496-1.28432.4102-0.05370.19970.41710.004-0.03410.0301-0.47120.0310.08780.12930.0023-0.01340.078-0.02940.125428.887148.86238.3519
61.072-0.22250.17591.2251-0.84544.71110.02450.07480.0037-0.22710.05250.2311-0.0103-0.2819-0.07690.0552-0.017-0.02610.0651-0.04510.117812.358233.051911.2219
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