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- PDB-2knc: Platelet integrin ALFAIIB-BETA3 transmembrane-cytoplasmic heteroc... -

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Basic information

Entry
Database: PDB / ID: 2knc
TitlePlatelet integrin ALFAIIB-BETA3 transmembrane-cytoplasmic heterocomplex
Components
  • Integrin alpha-IIb
  • Integrin beta-3Integrin beta 3
KeywordsCELL ADHESION / integrin / transmembrane signaling / protein structure / Cleavage on pair of basic residues / Disease mutation / Disulfide bond / Glycoprotein / Membrane / Pyrrolidone carboxylic acid / Receptor / Transmembrane / Host-virus interaction / Phosphoprotein
Function / homology
Function and homology information


tube development / regulation of serotonin uptake / positive regulation of adenylate cyclase-inhibiting opioid receptor signaling pathway / alpha9-beta1 integrin-ADAM8 complex / regulation of trophoblast cell migration / regulation of postsynaptic neurotransmitter receptor diffusion trapping / alphav-beta3 integrin-vitronectin complex / maintenance of postsynaptic specialization structure / regulation of extracellular matrix organization / platelet alpha granule membrane ...tube development / regulation of serotonin uptake / positive regulation of adenylate cyclase-inhibiting opioid receptor signaling pathway / alpha9-beta1 integrin-ADAM8 complex / regulation of trophoblast cell migration / regulation of postsynaptic neurotransmitter receptor diffusion trapping / alphav-beta3 integrin-vitronectin complex / maintenance of postsynaptic specialization structure / regulation of extracellular matrix organization / platelet alpha granule membrane / positive regulation of glomerular mesangial cell proliferation / integrin alphav-beta3 complex / negative regulation of lipoprotein metabolic process / alphav-beta3 integrin-PKCalpha complex / fibrinogen binding / glycinergic synapse / alphav-beta3 integrin-HMGB1 complex / vascular endothelial growth factor receptor 2 binding / blood coagulation, fibrin clot formation / negative regulation of lipid transport / negative regulation of low-density lipoprotein receptor activity / Elastic fibre formation / regulation of release of sequestered calcium ion into cytosol / cell-substrate junction assembly / mesodermal cell differentiation / angiogenesis involved in wound healing / alphav-beta3 integrin-IGF-1-IGF1R complex / platelet-derived growth factor receptor binding / filopodium membrane / extracellular matrix binding / positive regulation of fibroblast migration / positive regulation of vascular endothelial growth factor receptor signaling pathway / regulation of postsynaptic neurotransmitter receptor internalization / apolipoprotein A-I-mediated signaling pathway / regulation of bone resorption / wound healing, spreading of epidermal cells / apoptotic cell clearance / heterotypic cell-cell adhesion / positive regulation of cell adhesion mediated by integrin / integrin complex / Molecules associated with elastic fibres / cellular response to insulin-like growth factor stimulus / positive regulation of leukocyte migration / cell adhesion mediated by integrin / positive regulation of cell-matrix adhesion / smooth muscle cell migration / microvillus membrane / Syndecan interactions / negative chemotaxis / p130Cas linkage to MAPK signaling for integrins / cellular response to platelet-derived growth factor stimulus / cell-substrate adhesion / protein disulfide isomerase activity / positive regulation of smooth muscle cell migration / activation of protein kinase activity / positive regulation of osteoblast proliferation / TGF-beta receptor signaling activates SMADs / PECAM1 interactions / lamellipodium membrane / GRB2:SOS provides linkage to MAPK signaling for Integrins / negative regulation of macrophage derived foam cell differentiation / negative regulation of lipid storage / platelet-derived growth factor receptor signaling pathway / fibronectin binding / ECM proteoglycans / positive regulation of bone resorption / positive regulation of T cell migration / Integrin cell surface interactions / coreceptor activity / negative regulation of endothelial cell apoptotic process / positive regulation of substrate adhesion-dependent cell spreading / embryo implantation / positive regulation of endothelial cell proliferation / cell adhesion molecule binding / Integrin signaling / substrate adhesion-dependent cell spreading / cell-matrix adhesion / positive regulation of endothelial cell migration / protein kinase C binding / response to activity / Signal transduction by L1 / integrin-mediated signaling pathway / regulation of actin cytoskeleton organization / positive regulation of smooth muscle cell proliferation / Signaling by high-kinase activity BRAF mutants / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / MAP2K and MAPK activation / wound healing / cell-cell adhesion / platelet aggregation / platelet activation / ruffle membrane / VEGFA-VEGFR2 Pathway / cellular response to mechanical stimulus / positive regulation of angiogenesis / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / regulation of protein localization
Similarity search - Function
Bicelle-embedded integrin alpha(iib) transmembrane segment / Cytochrome c1, transmembrane anchor, C-terminal / Integrin beta, epidermal growth factor-like domain 1 / Integrin beta epidermal growth factor like domain 1 / Integrin beta subunit, cytoplasmic domain / Integrin beta cytoplasmic domain / Integrin_b_cyt / : / Integrin alpha Ig-like domain 3 / Integrin beta tail domain ...Bicelle-embedded integrin alpha(iib) transmembrane segment / Cytochrome c1, transmembrane anchor, C-terminal / Integrin beta, epidermal growth factor-like domain 1 / Integrin beta epidermal growth factor like domain 1 / Integrin beta subunit, cytoplasmic domain / Integrin beta cytoplasmic domain / Integrin_b_cyt / : / Integrin alpha Ig-like domain 3 / Integrin beta tail domain / Integrin beta subunit, tail / Integrin beta tail domain superfamily / Integrin_B_tail / Integrin beta subunit, VWA domain / Integrin beta subunit / Integrin beta N-terminal / Integrin beta chain VWA domain / Integrin plexin domain / Integrins beta chain cysteine-rich domain signature. / Integrin beta subunits (N-terminal portion of extracellular region) / Integrin alpha cytoplasmic region / EGF-like domain, extracellular / EGF-like domain / Integrin alpha-2 / Integrin alpha Ig-like domain 1 / : / Integrin alpha Ig-like domain 2 / Integrin alpha chain / Integrin alpha beta-propellor / Integrin alpha chain, C-terminal cytoplasmic region, conserved site / Integrins alpha chain signature. / FG-GAP repeat profile. / Integrin alpha (beta-propellor repeats). / FG-GAP repeat / FG-GAP repeat / Integrin domain superfamily / Integrin alpha, N-terminal / PSI domain / domain found in Plexins, Semaphorins and Integrins / von Willebrand factor A-like domain superfamily / EGF-like domain signature 2. / EGF-like domain signature 1. / Single alpha-helices involved in coiled-coils or other helix-helix interfaces / Up-down Bundle / Mainly Alpha
Similarity search - Domain/homology
Integrin beta-3 / Integrin alpha-IIb
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodSOLUTION NMR / simulated annealing
AuthorsYang, J. / Ma, Y. / Page, R.C. / Misra, S. / Plow, E.F. / Qin, J.
CitationJournal: Proc.Natl.Acad.Sci.USA / Year: 2009
Title: Structure of an integrin alphaIIb beta3 transmembrane-cytoplasmic heterocomplex provides insight into integrin activation.
Authors: Yang, J. / Ma, Y.Q. / Page, R.C. / Misra, S. / Plow, E.F. / Qin, J.
History
DepositionAug 20, 2009Deposition site: BMRB / Processing site: RCSB
Revision 1.0Sep 29, 2009Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Aug 10, 2011Group: Database references
Revision 1.3Feb 26, 2020Group: Data collection / Database references / Other
Category: database_2 / pdbx_database_status ...database_2 / pdbx_database_status / pdbx_nmr_software / pdbx_nmr_spectrometer / struct_ref_seq_dif
Item: _pdbx_database_status.status_code_cs / _pdbx_nmr_software.name ..._pdbx_database_status.status_code_cs / _pdbx_nmr_software.name / _pdbx_nmr_spectrometer.model / _struct_ref_seq_dif.details
Revision 1.4Aug 18, 2021Group: Data collection / Database references ...Data collection / Database references / Experimental preparation / Structure summary
Category: database_2 / pdbx_nmr_exptl ...database_2 / pdbx_nmr_exptl / pdbx_nmr_exptl_sample / pdbx_nmr_representative / pdbx_nmr_sample_details / pdbx_nmr_software / pdbx_nmr_spectrometer / struct
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_nmr_representative.selection_criteria / _pdbx_nmr_software.authors / _pdbx_nmr_software.classification / _pdbx_nmr_spectrometer.manufacturer / _pdbx_nmr_spectrometer.model / _struct.pdbx_model_details
Revision 1.5Jun 14, 2023Group: Other / Category: pdbx_database_status / Item: _pdbx_database_status.status_code_nmr_data
Revision 1.6May 8, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2 / Item: _database_2.pdbx_DOI
Remark 650HELIX DETERMINATION METHOD: AUTHOR DETERMINED

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Integrin alpha-IIb
B: Integrin beta-3


Theoretical massNumber of molelcules
Total (without water)14,8322
Polymers14,8322
Non-polymers00
Water0
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
NMR ensembles
DataCriteria
Number of conformers (submitted / calculated)20 / 98structures with the lowest energy
RepresentativeModel #1lowest energy

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Components

#1: Protein Integrin alpha-IIb / Platelet membrane glycoprotein IIb / GPalpha IIb / GPIIb / Integrin alpha-IIb heavy chain / ...Platelet membrane glycoprotein IIb / GPalpha IIb / GPIIb / Integrin alpha-IIb heavy chain / Integrin alpha-IIb light chain / form 1 / Integrin alpha-IIb light chain / form 2


Mass: 6057.068 Da / Num. of mol.: 1
Fragment: transmembrane and cytoplasmic domains, residues 991-1039
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ITGA2B, GP2B, ITGAB / Plasmid: pMAL-C2 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21-DE3 / References: UniProt: P08514
#2: Protein Integrin beta-3 / Integrin beta 3 / Platelet membrane glycoprotein IIIa / GPIIIa


Mass: 8775.271 Da / Num. of mol.: 1
Fragment: transmembrane and cytoplasmic domains, residues 715-788
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ITGB3, GP3A / Plasmid: pMAL-C2 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21-DE3 / References: UniProt: P05106

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Experimental details

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Experiment

ExperimentMethod: SOLUTION NMR
NMR experiment
Conditions-IDExperiment-IDSolution-IDType
1113D HNCO
1213D HNCA
1313D HN(CA)CB
1413D CBCA(CO)NH
1513D H(CCO)NH
1613D C(CO)NH
1733D 13C-15N NOESY
1833D 1H-15N NOESY
1943D 13C-15N NOESY
11023D HNCO
11123D HNCA
11223D HN(CA)CB
11323D CBCA(CO)NH
11423D H(CCO)NH
11523D C(CO)NH
11643D 1H-15N NOESY

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Sample preparation

Details
TypeSolution-IDContentsLabelSolvent system
solution10.2 MM [U-100% 13C U-100% 15N] AIIBTMCD, 0.6 MM B3TMCD, 50% CD3CN/50% H2O, 0.1% TFAsample_150% CD3CN/50% H2O
solution20.2 MM [U-100% 13C U-100% 15N] B3TMCD, 0.6 MM AIIBTMCD, 50% CD3CN/50% H2O, 0.1% TFAsample_250% CD3CN/50% H2O
solution30.4 MM [U-100% 2H U-100% 15N] B3TMCD, 1.2 MM AIIBTMCD, 50% CD3CN/50% H2O, 0.1% TFAsample_350% CD3CN/50% H2O
solution40.4 MM [U-100% 2H U-100% 15N] AIIBTMCD, 1.2 MM B3TMCD, 50% CD3CN/50% H2O, 0.1% TFAsample_450% CD3CN/50% H2O
Sample
Conc. (mg/ml)ComponentIsotopic labelingSolution-ID
0.2 mMAIIbTMCD-1[U-100% 13C; U-100% 15N]1
0.6 mMB3TMCD-2natural abundance1
0.2 mMB3TMCD-3[U-100% 13C; U-100% 15N]2
0.6 mMAIIbTMCD-4natural abundance2
0.4 mMB3TMCD-5[U-100% 2H; U-100% 15N]3
1.2 mMAIIbTMCD-6natural abundance3
0.4 mMAIIbTMCD-7[U-100% 2H; U-100% 15N]4
1.2 mMB3TMCD-8natural abundance4
0.1 %TFAnatural abundance1
0.1 %TFAnatural abundance2
0.1 %TFAnatural abundance3
0.1 %TFAnatural abundance4
Sample conditionsIonic strength: 0 / Pressure: AMBIENT / Temperature: 25 K

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NMR measurement

NMR spectrometer
TypeManufacturerModelField strength (MHz)Spectrometer-ID
Bruker AVANCEBrukerAVANCE6001
Bruker AVANCEBrukerAVANCE8002
Bruker AVANCEBrukerAVANCE9003

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Processing

NMR software
NameVersionDeveloperClassification
X-PLOR NIH2.15.0Schwieters, Kuszewski, Tjandra and Clorerefinement
X-PLOR NIH2.15.0Schwieters, Kuszewski, Tjandra and Clorestructure solution
NMRPipe2.4Delaglio, Grzesiek, Vuister, Zhu, Pfeifer and Baxprocessing
PASAXu, Wang, Yang, Vaynberg, Qinchemical shift assignment
PROCHECKLaskowski, MacArthur, Smith, Jones, Hutchinson, Morris, Moss and Thodata analysis
RefinementMethod: simulated annealing / Software ordinal: 1
NMR constraintsNOE constraints total: 2100 / NOE intraresidue total count: 665 / NOE long range total count: 83 / NOE medium range total count: 688 / NOE sequential total count: 664 / Hydrogen bond constraints total count: 213 / Protein phi angle constraints total count: 74 / Protein psi angle constraints total count: 74
NMR representativeSelection criteria: lowest energy
NMR ensembleConformer selection criteria: structures with the lowest energy
Conformers calculated total number: 98 / Conformers submitted total number: 20

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