[English] 日本語
Yorodumi
- PDB-3qs9: Crystal structure of a human Flt3 ligand-receptor ternary complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3qs9
TitleCrystal structure of a human Flt3 ligand-receptor ternary complex
Components
  • FL cytokine receptor
  • SL cytokine
KeywordsCYTOKINE/SIGNALING PROTEIN / immunoglobulin-like domain / four-helical bundle cytokine / hematopoietic cytokine-receptor complex / cell surface / extracellular complex / receptor tyrosine kinase / CYTOKINE-SIGNALING PROTEIN complex
Function / homology
Function and homology information


FLT3 mutants bind TKIs / KW2449-resistant FLT3 mutants / semaxanib-resistant FLT3 mutants / crenolanib-resistant FLT3 mutants / gilteritinib-resistant FLT3 mutants / lestaurtinib-resistant FLT3 mutants / midostaurin-resistant FLT3 mutants / pexidartinib-resistant FLT3 mutants / ponatinib-resistant FLT3 mutants / quizartinib-resistant FLT3 mutants ...FLT3 mutants bind TKIs / KW2449-resistant FLT3 mutants / semaxanib-resistant FLT3 mutants / crenolanib-resistant FLT3 mutants / gilteritinib-resistant FLT3 mutants / lestaurtinib-resistant FLT3 mutants / midostaurin-resistant FLT3 mutants / pexidartinib-resistant FLT3 mutants / ponatinib-resistant FLT3 mutants / quizartinib-resistant FLT3 mutants / sorafenib-resistant FLT3 mutants / sunitinib-resistant FLT3 mutants / tandutinib-resistant FLT3 mutants / linifanib-resistant FLT3 mutants / tamatinib-resistant FLT3 mutants / leukocyte homeostasis / lymphocyte proliferation / pro-B cell differentiation / common myeloid progenitor cell proliferation / dendritic cell differentiation / vascular endothelial growth factor receptor activity / phosphatidylinositol 3-kinase activator activity / STAT5 Activation / nuclear glucocorticoid receptor binding / myeloid progenitor cell differentiation / FLT3 signaling through SRC family kinases / cellular response to glucocorticoid stimulus / embryonic hemopoiesis / cytokine receptor activity / STAT5 activation downstream of FLT3 ITD mutants / growth factor binding / cellular response to cytokine stimulus / hemopoiesis / PI3K Cascade / animal organ regeneration / Signaling by FLT3 ITD and TKD mutants / positive regulation of tyrosine phosphorylation of STAT protein / FLT3 signaling by CBL mutants / cell surface receptor protein tyrosine kinase signaling pathway / response to organonitrogen compound / Negative regulation of FLT3 / FLT3 Signaling / transmembrane receptor protein tyrosine kinase activity / B cell differentiation / cytokine activity / positive regulation of MAP kinase activity / receptor protein-tyrosine kinase / receptor tyrosine kinase binding / cytokine-mediated signaling pathway / peptidyl-tyrosine phosphorylation / Constitutive Signaling by Aberrant PI3K in Cancer / : / PIP3 activates AKT signaling / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RAF/MAP kinase cascade / regulation of apoptotic process / protein tyrosine kinase activity / positive regulation of MAPK cascade / protein autophosphorylation / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / endosome membrane / endoplasmic reticulum lumen / signaling receptor binding / positive regulation of cell population proliferation / protein-containing complex binding / cell surface / endoplasmic reticulum / signal transduction / extracellular space / extracellular region / ATP binding / membrane / plasma membrane / cytosol
Similarity search - Function
Flt3 ligand / flt3 ligand / Tyrosine-protein kinase, receptor class III, conserved site / Receptor tyrosine kinase class III signature. / Four-helical cytokine-like, core / Immunoglobulin / Immunoglobulin domain / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. ...Flt3 ligand / flt3 ligand / Tyrosine-protein kinase, receptor class III, conserved site / Receptor tyrosine kinase class III signature. / Four-helical cytokine-like, core / Immunoglobulin / Immunoglobulin domain / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Immunoglobulin-like fold / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
Receptor-type tyrosine-protein kinase FLT3 / Fms-related tyrosine kinase 3 ligand
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 7.8 Å
AuthorsVerstraete, K. / Savvides, S.N.
Citation
Journal: Blood / Year: 2011
Title: Structural insights into the extracellular assembly of the hematopoietic Flt3 signaling complex.
Authors: Verstraete, K. / Vandriessche, G. / Januar, M. / Elegheert, J. / Shkumatov, A.V. / Desfosses, A. / Van Craenenbroeck, K. / Svergun, D.I. / Gutsche, I. / Vergauwen, B. / Savvides, S.N.
#1: Journal: To be Published
Title: Inducible production of human Flt3 ectodomain variants in mammalian cells and preliminary crystallographic analysis of Flt3 ligand-receptor complexes
Authors: Verstraete, K. / Vandriessche, G. / Januar, M. / Elegheert, J. / Shkumatov, A. / Desfosses, A. / Van Craenenbroeck, K. / Svergun, D. / Gutsche, I. / Vergauwen, B. / Savvides, S.N.
#2: Journal: Protein J. / Year: 2009
Title: Efficient production of bioactive recombinant human Flt3 ligand in E. coli.
Authors: Verstraete, K. / Koch, S. / Ertugrul, S. / Vandenberghe, I. / Aerts, M. / Vandriessche, G. / Thiede, C. / Savvides, S.N.
History
DepositionFeb 20, 2011Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 16, 2011Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Jul 20, 2011Group: Database references
Revision 1.3Mar 31, 2021Group: Database references / Category: struct_ref_seq_dif / Item: _struct_ref_seq_dif.details
Revision 1.4Sep 13, 2023Group: 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
A: SL cytokine
B: SL cytokine
C: SL cytokine
D: SL cytokine
E: FL cytokine receptor
F: FL cytokine receptor
G: FL cytokine receptor
H: FL cytokine receptor


Theoretical massNumber of molelcules
Total (without water)301,6298
Polymers301,6298
Non-polymers00
Water00
1
C: SL cytokine
D: SL cytokine
G: FL cytokine receptor
H: FL cytokine receptor


Theoretical massNumber of molelcules
Total (without water)150,8154
Polymers150,8154
Non-polymers00
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
A: SL cytokine
B: SL cytokine
E: FL cytokine receptor
F: FL cytokine receptor


Theoretical massNumber of molelcules
Total (without water)150,8154
Polymers150,8154
Non-polymers00
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)124.750, 153.550, 133.870
Angle α, β, γ (deg.)90.000, 94.570, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein
SL cytokine / Flt3 ligand / Fms-related tyrosine kinase 3 ligand / Flt3L


Mass: 15873.217 Da / Num. of mol.: 4 / Fragment: extracellular domain (UNP residues 27-160)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FLT3LG / Plasmid: pET15B / Production host: Escherichia coli (E. coli) / Strain (production host): ROSETTA-GAMI(DE3) / References: UniProt: P49771
#2: Protein
FL cytokine receptor / Tyrosine-protein kinase receptor FLT3 / Fms-like tyrosine kinase 3 / FLT-3 / Stem cell tyrosine ...Tyrosine-protein kinase receptor FLT3 / Fms-like tyrosine kinase 3 / FLT-3 / Stem cell tyrosine kinase 1 / STK-1


Mass: 59534.137 Da / Num. of mol.: 4 / Fragment: extracellular domain (UNP residues 27-540)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FLT3, STK1 / Plasmid: pcDNA4/TO / Cell line (production host): HEK 293 / Production host: Homo sapiens (human) / Strain (production host): GNTI-
References: UniProt: P36888, receptor protein-tyrosine kinase

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 4.24 Å3/Da / Density % sol: 70.97 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 7
Details: 12-14% w/v PEG3350, 0.2 M lithium citrate, 0.1 M TRIS-HCl, pH 7.0, VAPOR DIFFUSION, SITTING DROP, temperature 293.0K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID23-1 / Wavelength: 1.0762
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: May 1, 2009
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.0762 Å / Relative weight: 1
ReflectionResolution: 7.8→35 Å / Num. all: 5853 / Num. obs: 5656 / % possible obs: 96.6 % / Observed criterion σ(I): -3 / Redundancy: 3.38 % / Biso Wilson estimate: 401 Å2 / Rmerge(I) obs: 0.128 / Net I/σ(I): 9.08
Reflection shellResolution: 7.8→8 Å / Redundancy: 3.2 % / Rmerge(I) obs: 0.807 / Mean I/σ(I) obs: 1.9 / % possible all: 92.9

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
XSCALEdata scaling
PHASERphasing
BUSTER-TNTBUSTER 2.8.0refinement
PDB_EXTRACT3.1data extraction
BUSTER2.8.0refinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRIES 1ETE,2E9W,3QS7
Resolution: 7.8→35 Å / Cor.coef. Fo:Fc: 0.7108 / Cor.coef. Fo:Fc free: 0.611 / Occupancy max: 1 / Occupancy min: 1 / Isotropic thermal model: ISOTROPIC / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.3462 565 9.99 %RANDOM
Rwork0.3367 ---
obs0.3376 5655 96.6 %-
all-5853 --
Displacement parametersBiso max: 469.34 Å2 / Biso mean: 363.75 Å2 / Biso min: 288.74 Å2
Baniso -1Baniso -2Baniso -3
1--3.0141 Å20 Å2-17.5962 Å2
2--35.2075 Å20 Å2
3----32.1934 Å2
Refine analyzeLuzzati coordinate error obs: 2.415 Å
Refinement stepCycle: LAST / Resolution: 7.8→35 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms13542 0 0 0 13542
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.01213846HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.3619054HARMONIC2
X-RAY DIFFRACTIONt_omega_torsion2.58
X-RAY DIFFRACTIONt_other_torsion18.66
X-RAY DIFFRACTIONt_dihedral_angle_d3800SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes144HARMONIC2
X-RAY DIFFRACTIONt_gen_planes2236HARMONIC5
X-RAY DIFFRACTIONt_it13846HARMONIC20
X-RAY DIFFRACTIONt_chiral_improper_torsion2101SEMIHARMONIC5
X-RAY DIFFRACTIONt_utility_distance4HARMONIC1
X-RAY DIFFRACTIONt_ideal_dist_contact14999SEMIHARMONIC4
LS refinement shellResolution: 7.8→8.72 Å / Total num. of bins used: 5
RfactorNum. reflection% reflection
Rfree0.3129 159 9.96 %
Rwork0.3337 1437 -
all0.3316 1596 -
obs-1596 -

+
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://pdbjlvh1.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