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- PDB-7kn0: Structure of the integrin aIIb(W968V)b3 transmembrane complex -

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Basic information

Entry
Database: PDB / ID: 7kn0
TitleStructure of the integrin aIIb(W968V)b3 transmembrane complex
Components
  • Integrin alpha-IIb
  • Integrin beta-3Integrin beta 3
KeywordsCELL ADHESION / safeguarding motif / transmembrane complex
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
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 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.
Similarity search - Domain/homology
Integrin beta-3 / Integrin alpha-IIb
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodSOLUTION NMR / simulated annealing
AuthorsSitu, A.J. / Kim, J. / An, W. / Kim, C. / Ulmer, T.S.
Funding support United States, 1items
OrganizationGrant numberCountry
American Heart Association18TPA34170481 United States
CitationJournal: J.Mol.Biol. / Year: 2021
Title: Insight Into Pathological Integrin alpha IIb beta 3 Activation From Safeguarding The Inactive State.
Authors: Situ, A.J. / Kim, J. / An, W. / Kim, C. / Ulmer, T.S.
History
DepositionNov 3, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 15, 2021Provider: repository / Type: Initial release
Revision 1.1Jun 14, 2023Group: Other / Category: pdbx_database_status / Item: _pdbx_database_status.status_code_nmr_data

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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)9,5302
Polymers9,5302
Non-polymers00
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: isothermal titration calorimetry
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area1640 Å2
ΔGint-23 kcal/mol
Surface area7490 Å2
NMR ensembles
DataCriteria
Number of conformers (submitted / calculated)21 / 21all calculated structures submitted
RepresentativeModel #1minimized average structure

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Components

#1: Protein/peptide Integrin alpha-IIb / GPalpha IIb / GPIIb / Platelet membrane glycoprotein IIb


Mass: 4753.871 Da / Num. of mol.: 1 / Mutation: A963G, W968V
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ITGA2B, GP2B, ITGAB / Production host: Escherichia coli (E. coli) / References: UniProt: P08514
#2: Protein/peptide Integrin beta-3 / Integrin beta 3 / Platelet membrane glycoprotein IIIa / GPIIIa


Mass: 4775.867 Da / Num. of mol.: 1 / Mutation: C686S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ITGB3, GP3A / Production host: Escherichia coli (E. coli) / References: UniProt: P05106

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Experimental details

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Experiment

ExperimentMethod: SOLUTION NMR
NMR experiment
Conditions-IDExperiment-IDSolution-IDSample stateSpectrometer-IDType
111isotropic12D 1H-15N HSQC
121isotropic13D HN(CA)CB
131isotropic13D HNCA

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Sample preparation

DetailsType: bicelle
Contents: 0.8 mM [U-100% 13C; U-100% 15N; U-80% 2H] transmembrane complex, 93% H2O/7% D2O
Label: 2H13C15N_sample / Solvent system: 93% H2O/7% D2O
SampleConc.: 0.8 mM / Component: transmembrane complex / Isotopic labeling: [U-100% 13C; U-100% 15N; U-80% 2H]
Sample conditionsDetails: 25 mM HEPES / Ionic strength: 25 mM / Label: condition_1 / pH: 7.4 / Pressure: 1 atm / Temperature: 313.2 K

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NMR measurement

NMR spectrometerType: Bruker AVANCE / Manufacturer: Bruker / Model: AVANCE / Field strength: 700 MHz

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Processing

NMR software
NameDeveloperClassification
X-PLOR NIHSchwieters, Kuszewski, Tjandra and Clorestructure calculation
CARAKeller and Wuthrichchemical shift assignment
NMRPipeDelaglio, Grzesiek, Vuister, Zhu, Pfeifer and Baxdata analysis
RefinementMethod: simulated annealing / Software ordinal: 1
NMR representativeSelection criteria: minimized average structure
NMR ensembleConformer selection criteria: all calculated structures submitted
Conformers calculated total number: 21 / Conformers submitted total number: 21

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