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- PDB-5oc7: Crystal structure of the pleckstrin-homology domain of Bcr-Abl in... -
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Open data
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Basic information
Entry | Database: PDB / ID: 5oc7 | ||||||
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Title | Crystal structure of the pleckstrin-homology domain of Bcr-Abl in complex with monobody Mb(Bcr-PH_4). | ||||||
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![]() | SIGNALING PROTEIN / pleckstrin-homology / monobody / Bcr-Abl / phosphoinositide-binding | ||||||
Function / homology | ![]() negative regulation of respiratory burst / : / negative regulation of cellular extravasation / negative regulation of macrophage migration / negative regulation of blood vessel remodeling / negative regulation of neutrophil degranulation / macrophage migration / neutrophil degranulation / intracellular protein transmembrane transport / renal system process ...negative regulation of respiratory burst / : / negative regulation of cellular extravasation / negative regulation of macrophage migration / negative regulation of blood vessel remodeling / negative regulation of neutrophil degranulation / macrophage migration / neutrophil degranulation / intracellular protein transmembrane transport / renal system process / regulation of vascular permeability / regulation of Rho protein signal transduction / focal adhesion assembly / definitive hemopoiesis / Signaling by cytosolic FGFR1 fusion mutants / activation of GTPase activity / regulation of small GTPase mediated signal transduction / inner ear morphogenesis / RHOB GTPase cycle / small GTPase-mediated signal transduction / RHOC GTPase cycle / CDC42 GTPase cycle / neuromuscular process controlling balance / homeostasis of number of cells / RHOA GTPase cycle / negative regulation of reactive oxygen species metabolic process / RAC2 GTPase cycle / RAC3 GTPase cycle / phagocytosis / positive regulation of phagocytosis / keratinocyte differentiation / RAC1 GTPase cycle / Signaling by FGFR1 in disease / GTPase activator activity / guanyl-nucleotide exchange factor activity / Schaffer collateral - CA1 synapse / modulation of chemical synaptic transmission / brain development / negative regulation of inflammatory response / actin cytoskeleton organization / cellular response to lipopolysaccharide / protein tyrosine kinase activity / dendritic spine / postsynaptic density / non-specific serine/threonine protein kinase / regulation of cell cycle / axon / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / glutamatergic synapse / signal transduction / protein-containing complex / extracellular exosome / ATP binding / membrane / plasma membrane / cytosol Similarity search - Function | ||||||
Biological species | ![]() synthetic construct (others) | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Reckel, S. / Reynaud, A. / Pojer, F. / Hantschel, O. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase. Authors: Sina Reckel / Charlotte Gehin / Delphine Tardivon / Sandrine Georgeon / Tim Kükenshöner / Frank Löhr / Akiko Koide / Lena Buchner / Alejandro Panjkovich / Aline Reynaud / Sara Pinho / ...Authors: Sina Reckel / Charlotte Gehin / Delphine Tardivon / Sandrine Georgeon / Tim Kükenshöner / Frank Löhr / Akiko Koide / Lena Buchner / Alejandro Panjkovich / Aline Reynaud / Sara Pinho / Barbara Gerig / Dmitri Svergun / Florence Pojer / Peter Güntert / Volker Dötsch / Shohei Koide / Anne-Claude Gavin / Oliver Hantschel / ![]() ![]() ![]() ![]() Abstract: The two isoforms of the Bcr-Abl tyrosine kinase, p210 and p190, are associated with different leukemias and have a dramatically different signaling network, despite similar kinase activity. To ...The two isoforms of the Bcr-Abl tyrosine kinase, p210 and p190, are associated with different leukemias and have a dramatically different signaling network, despite similar kinase activity. To provide a molecular rationale for these observations, we study the Dbl-homology (DH) and Pleckstrin-homology (PH) domains of Bcr-Abl p210, which constitute the only structural differences to p190. Here we report high-resolution structures of the DH and PH domains and characterize conformations of the DH-PH unit in solution. Our structural and functional analyses show no evidence that the DH domain acts as a guanine nucleotide exchange factor, whereas the PH domain binds to various phosphatidylinositol-phosphates. PH-domain mutants alter subcellular localization and result in decreased interactions with p210-selective interaction partners. Hence, the PH domain, but not the DH domain, plays an important role in the formation of the differential p210 and p190 Bcr-Abl signaling networks. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 175.7 KB | Display | ![]() |
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PDB format | ![]() | 142.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 876.8 KB | Display | ![]() |
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Full document | ![]() | 881 KB | Display | |
Data in XML | ![]() | 20.5 KB | Display | |
Data in CIF | ![]() | 28.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 5n6rC ![]() 5n7eC ![]() 2dfkS S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 15643.062 Da / Num. of mol.: 2 / Mutation: delta 770-829,delta 770-829 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: P11274, non-specific serine/threonine protein kinase #2: Protein | Mass: 9632.773 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: ![]() ![]() #3: Chemical | ChemComp-GOL / #4: Chemical | ChemComp-IP2 / | #5: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.47 Å3/Da / Density % sol: 50 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, sitting drop Details: 0.1 M Potassium thiocyanate, 30% (w/v) PEG MME 2000 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS 2M / Detector: PIXEL / Date: May 19, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.99987 Å / Relative weight: 1 |
Reflection | Resolution: 1.652→33.68 Å / Num. obs: 49951 / % possible obs: 97.13 % / Redundancy: 4.899 % / Rmerge(I) obs: 0.03096 / Rpim(I) all: 0.01554 / Rrim(I) all: 0.03473 / Net I/σ(I): 23.01 |
Reflection shell | Resolution: 1.652→1.711 Å / Rmerge(I) obs: 0.6334 / Num. unique obs: 4899 / Rpim(I) all: 0.3281 / Rrim(I) all: 0.7159 / % possible all: 96.1 |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 2DFK Resolution: 1.652→33.68 Å / SU ML: 0.2 / Cross valid method: NONE / σ(F): 1.97 / Phase error: 21.66
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.652→33.68 Å
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Refine LS restraints |
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LS refinement shell |
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