[English] 日本語
Yorodumi
- PDB-5oc7: Crystal structure of the pleckstrin-homology domain of Bcr-Abl in... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5oc7
TitleCrystal structure of the pleckstrin-homology domain of Bcr-Abl in complex with monobody Mb(Bcr-PH_4).
Components
  • Breakpoint cluster region protein,pleckstrin-homology domain of Bcr-Abl
  • monobody Mb(Bcr-PH_4)
KeywordsSIGNALING PROTEIN / pleckstrin-homology / monobody / Bcr-Abl / phosphoinositide-binding
Function / homology
Function and homology information


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 / small GTPase-mediated signal transduction / RHOB GTPase cycle / 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 / brain development / modulation of chemical synaptic transmission / negative regulation of inflammatory response / actin cytoskeleton organization / protein tyrosine kinase activity / cellular response to lipopolysaccharide / 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
PH domain / Bcr-Abl oncoprotein oligomerisation / Bcr-Abl oncoprotein oligomerisation domain superfamily / Bcr-Abl oncoprotein oligomerisation domain / Abr/Bcr / Guanine-nucleotide dissociation stimulator, CDC24, conserved site / Dbl homology (DH) domain signature. / Rho GTPase-activating protein domain / RhoGAP domain / Rho GTPase-activating proteins domain profile. ...PH domain / Bcr-Abl oncoprotein oligomerisation / Bcr-Abl oncoprotein oligomerisation domain superfamily / Bcr-Abl oncoprotein oligomerisation domain / Abr/Bcr / Guanine-nucleotide dissociation stimulator, CDC24, conserved site / Dbl homology (DH) domain signature. / Rho GTPase-activating protein domain / RhoGAP domain / Rho GTPase-activating proteins domain profile. / GTPase-activator protein for Rho-like GTPases / Rho GTPase activation protein / Dbl homology (DH) domain superfamily / RhoGEF domain / Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases / Dbl homology (DH) domain / Dbl homology (DH) domain profile. / C2 domain / Protein kinase C conserved region 2 (CalB) / C2 domain / C2 domain profile. / C2 domain superfamily / PH domain profile. / Pleckstrin homology domain. / Pleckstrin homology domain / PH-like domain superfamily / Immunoglobulins / Immunoglobulin-like / Sandwich / Mainly Beta
Similarity search - Domain/homology
D-MYO-INOSITOL-4,5-BISPHOSPHATE / Breakpoint cluster region protein
Similarity search - Component
Biological speciesHomo sapiens (human)
synthetic construct (others)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.652 Å
AuthorsReckel, S. / Reynaud, A. / Pojer, F. / Hantschel, O.
Funding support Switzerland, 1items
OrganizationGrant numberCountry
Swiss National Science Foundation31003A_140913 Switzerland
CitationJournal: Nat Commun / Year: 2017
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.
History
DepositionJun 29, 2017Deposition site: PDBE / Processing site: PDBE
Revision 1.0Dec 27, 2017Provider: repository / Type: Initial release
Revision 1.1Jan 17, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
D: Breakpoint cluster region protein,pleckstrin-homology domain of Bcr-Abl
A: Breakpoint cluster region protein,pleckstrin-homology domain of Bcr-Abl
C: monobody Mb(Bcr-PH_4)
B: monobody Mb(Bcr-PH_4)
hetero molecules


Theoretical massNumber of molelcules
Total (without water)51,53612
Polymers50,5524
Non-polymers9858
Water4,558253
1
A: Breakpoint cluster region protein,pleckstrin-homology domain of Bcr-Abl
C: monobody Mb(Bcr-PH_4)
hetero molecules


Theoretical massNumber of molelcules
Total (without water)25,6446
Polymers25,2762
Non-polymers3684
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
D: Breakpoint cluster region protein,pleckstrin-homology domain of Bcr-Abl
hetero molecules


Theoretical massNumber of molelcules
Total (without water)16,0753
Polymers15,6431
Non-polymers4322
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
3


  • Idetical with deposited unit
  • defined by software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3920 Å2
ΔGint-4 kcal/mol
Surface area21400 Å2
MethodPISA
4
B: monobody Mb(Bcr-PH_4)
hetero molecules


Theoretical massNumber of molelcules
Total (without water)9,8173
Polymers9,6331
Non-polymers1842
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)29.683, 62.606, 67.378
Angle α, β, γ (deg.)62.74, 84.77, 89.29
Int Tables number1
Space group name H-MP1

-
Components

#1: Protein Breakpoint cluster region protein,pleckstrin-homology domain of Bcr-Abl / Renal carcinoma antigen NY-REN-26


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.) Homo sapiens (human) / Gene: BCR, BCR1, D22S11 / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: P11274, non-specific serine/threonine protein kinase
#2: Protein monobody Mb(Bcr-PH_4)


Mass: 9632.773 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) synthetic construct (others) / Production host: Escherichia coli BL21(DE3) (bacteria)
#3: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL / Glycerol


Mass: 92.094 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: C3H8O3
#4: Chemical ChemComp-IP2 / D-MYO-INOSITOL-4,5-BISPHOSPHATE


Mass: 340.116 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C6H14O12P2 / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 253 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.47 Å3/Da / Density % sol: 50 %
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop
Details: 0.1 M Potassium thiocyanate, 30% (w/v) PEG MME 2000

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06DA / Wavelength: 0.99987 Å
DetectorType: DECTRIS PILATUS 2M / Detector: PIXEL / Date: May 19, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.99987 Å / Relative weight: 1
ReflectionResolution: 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 shellResolution: 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

-
Processing

Software
NameVersionClassification
PHENIX(1.11.1_2575: ???)refinement
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2DFK

2dfk


Resolution: 1.652→33.68 Å / SU ML: 0.2 / Cross valid method: NONE / σ(F): 1.97 / Phase error: 21.66
RfactorNum. reflection% reflection
Rfree0.2043 2001 4 %
Rwork0.1742 --
obs0.1754 49948 95.56 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Refinement stepCycle: LAST / Resolution: 1.652→33.68 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3212 0 62 253 3527
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0113420
X-RAY DIFFRACTIONf_angle_d1.0764646
X-RAY DIFFRACTIONf_dihedral_angle_d17.9472036
X-RAY DIFFRACTIONf_chiral_restr0.062529
X-RAY DIFFRACTIONf_plane_restr0.007576
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.6516-1.67170.28241420.27243218X-RAY DIFFRACTION94
1.6717-1.69290.29191430.27913388X-RAY DIFFRACTION95
1.6929-1.71520.3191360.26953295X-RAY DIFFRACTION94
1.7152-1.73870.26981240.2553467X-RAY DIFFRACTION94
1.7387-1.76350.25581470.24723234X-RAY DIFFRACTION95
1.7635-1.78980.28151390.23993375X-RAY DIFFRACTION96
1.7898-1.81780.24381400.22413333X-RAY DIFFRACTION95
1.8178-1.84760.29121340.22613380X-RAY DIFFRACTION94
1.8476-1.87950.25821360.22723360X-RAY DIFFRACTION95
1.8795-1.91360.25181410.22023285X-RAY DIFFRACTION95
1.9136-1.95040.2391310.21083443X-RAY DIFFRACTION95
1.9504-1.99020.20271400.20663347X-RAY DIFFRACTION95
1.9902-2.03350.2481470.19263353X-RAY DIFFRACTION96
2.0335-2.08080.24151340.19893380X-RAY DIFFRACTION95
2.0808-2.13280.23651440.1873372X-RAY DIFFRACTION95
2.1328-2.19050.23121360.1933386X-RAY DIFFRACTION96
2.1905-2.25490.2191530.18493388X-RAY DIFFRACTION95
2.2549-2.32770.19221300.17683399X-RAY DIFFRACTION96
2.3277-2.41090.21091440.17713380X-RAY DIFFRACTION96
2.4109-2.50740.22221480.17913374X-RAY DIFFRACTION96
2.5074-2.62140.25381340.17233389X-RAY DIFFRACTION96
2.6214-2.75960.20591470.17373384X-RAY DIFFRACTION95
2.7596-2.93240.19741440.17163425X-RAY DIFFRACTION97
2.9324-3.15860.21131310.16313371X-RAY DIFFRACTION97
3.1586-3.47620.21251490.1623390X-RAY DIFFRACTION96
3.4762-3.97860.18271470.14953405X-RAY DIFFRACTION97
3.9786-5.00990.13821440.13013417X-RAY DIFFRACTION97
5.0099-33.69080.20761460.18813498X-RAY DIFFRACTION99

+
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