[English] 日本語
Yorodumi
- PDB-4bsk: Crystal structure of VEGF-C in complex with VEGFR-3 domains D1-2 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4bsk
TitleCrystal structure of VEGF-C in complex with VEGFR-3 domains D1-2
Components
  • VASCULAR ENDOTHELIAL GROWTH FACTOR C
  • VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 3
KeywordsTRANSFERASE/HORMONE / TRANSFERASE-HORMONE COMPLEX / TRANSFERASE / LYMPHANGIOGENESIS / ANGIOGENESIS / IG DOMAIN / GLYCOPROTEIN / RECEPTOR TYROSINE KINASE / DIMERIZATION
Function / homology
Function and homology information


vascular endothelial growth factor receptor 3 binding / substrate-dependent cell migration / regulation of blood vessel remodeling / positive regulation of lymphangiogenesis / VEGF ligand-receptor interactions / positive regulation of mast cell chemotaxis / morphogenesis of embryonic epithelium / lymphangiogenesis / regulation of vascular endothelial growth factor receptor signaling pathway / positive regulation of mesenchymal stem cell proliferation ...vascular endothelial growth factor receptor 3 binding / substrate-dependent cell migration / regulation of blood vessel remodeling / positive regulation of lymphangiogenesis / VEGF ligand-receptor interactions / positive regulation of mast cell chemotaxis / morphogenesis of embryonic epithelium / lymphangiogenesis / regulation of vascular endothelial growth factor receptor signaling pathway / positive regulation of mesenchymal stem cell proliferation / VEGF binds to VEGFR leading to receptor dimerization / vascular endothelial growth factor receptor activity / lymph vessel development / induction of positive chemotaxis / respiratory system process / vasculature development / sprouting angiogenesis / blood vessel morphogenesis / NOTCH4 Intracellular Domain Regulates Transcription / vascular endothelial growth factor signaling pathway / lung alveolus development / growth factor binding / positive regulation of neuroblast proliferation / chemoattractant activity / positive regulation of vascular endothelial growth factor production / positive regulation of cell division / positive regulation of glial cell proliferation / cellular response to vascular endothelial growth factor stimulus / positive regulation of blood vessel endothelial cell migration / vascular endothelial growth factor receptor signaling pathway / negative regulation of osteoblast differentiation / glial cell proliferation / negative regulation of blood pressure / positive regulation of endothelial cell proliferation / transmembrane receptor protein tyrosine kinase activity / positive regulation of endothelial cell migration / cell surface receptor protein tyrosine kinase signaling pathway / platelet alpha granule lumen / peptidyl-tyrosine phosphorylation / cellular response to leukemia inhibitory factor / animal organ morphogenesis / positive regulation of epithelial cell proliferation / positive regulation of protein secretion / positive regulation of JNK cascade / growth factor activity / receptor protein-tyrosine kinase / positive regulation of protein phosphorylation / positive regulation of angiogenesis / cell migration / Platelet degranulation / protein autophosphorylation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / protein phosphatase binding / response to hypoxia / positive regulation of ERK1 and ERK2 cascade / receptor complex / positive regulation of MAPK cascade / positive regulation of cell migration / response to xenobiotic stimulus / positive regulation of cell population proliferation / negative regulation of apoptotic process / signal transduction / protein homodimerization activity / extracellular space / extracellular region / ATP binding / nucleus / membrane / plasma membrane / cytoplasm
Similarity search - Function
CXCXC repeat / CXCXC repeat / VEGFR-2, transmembrane domain / : / : / : / VEGFR-2 Transmembrane domain / Vascular endothelial growth factor receptor 1-like, Ig-like domain / VEGFR1-3, N-terminal Ig-like domain / VEGFR-1-like, immunoglobulin-like domain ...CXCXC repeat / CXCXC repeat / VEGFR-2, transmembrane domain / : / : / : / VEGFR-2 Transmembrane domain / Vascular endothelial growth factor receptor 1-like, Ig-like domain / VEGFR1-3, N-terminal Ig-like domain / VEGFR-1-like, immunoglobulin-like domain / PDGF/VEGF domain / Platelet-derived growth factor, conserved site / PDGF/VEGF domain / Platelet-derived growth factor (PDGF) family signature. / Platelet-derived growth factor (PDGF) family profile. / Platelet-derived and vascular endothelial growth factors (PDGF, VEGF) family / Tyrosine-protein kinase, receptor class III, conserved site / Receptor tyrosine kinase class III signature. / Cystine-knot cytokine / Immunoglobulin domain / Immunoglobulin I-set / Immunoglobulin I-set domain / : / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Immunoglobulin subtype / Immunoglobulin / Tyrosine-protein kinase, active site / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / 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
Vascular endothelial growth factor receptor 3 / Vascular endothelial growth factor C
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MIRAS / Resolution: 4.201 Å
AuthorsLeppanen, V.M. / Tvorogov, D. / Kisko, K. / Prota, A.E. / Jeltsch, M. / Anisimov, A. / Markovic-Mueller, S. / Stuttfeld, E. / Goldie, K.N. / Ballmer-Hofer, K. / Alitalo, K.
CitationJournal: Proc.Natl.Acad.Sci.USA / Year: 2013
Title: Structural and Mechanistic Insights Into Vegfr-3 Ligand Binding and Activation
Authors: Leppanen, V.-M. / Tvorogov, D. / Kisko, K. / Prota, A.E. / Jeltsch, M. / Anisimov, A. / Markovic-Mueller, S. / Stuttfeld, E. / Goldie, K.N. / Ballmer-Hofer, K. / Alitalo, K.
History
DepositionJun 10, 2013Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jul 31, 2013Provider: repository / Type: Initial release
Revision 1.1Aug 21, 2013Group: Database references
Revision 1.2Aug 28, 2013Group: Derived calculations
Revision 2.0Apr 11, 2018Group: Advisory / Atomic model ...Advisory / Atomic model / Data collection / Derived calculations
Category: atom_site / database_PDB_caveat ...atom_site / database_PDB_caveat / pdbx_nonpoly_scheme / pdbx_struct_sheet_hbond / pdbx_validate_chiral / struct_conf / struct_conn / struct_sheet / struct_sheet_order / struct_sheet_range / struct_site
Item: _atom_site.auth_seq_id / _pdbx_nonpoly_scheme.pdb_seq_num ..._atom_site.auth_seq_id / _pdbx_nonpoly_scheme.pdb_seq_num / _pdbx_struct_sheet_hbond.range_1_auth_atom_id / _pdbx_struct_sheet_hbond.range_1_auth_comp_id / _pdbx_struct_sheet_hbond.range_1_auth_seq_id / _pdbx_struct_sheet_hbond.range_1_label_atom_id / _pdbx_struct_sheet_hbond.range_1_label_comp_id / _pdbx_struct_sheet_hbond.range_1_label_seq_id / _pdbx_struct_sheet_hbond.range_2_auth_atom_id / _pdbx_struct_sheet_hbond.range_2_auth_comp_id / _pdbx_struct_sheet_hbond.range_2_auth_seq_id / _pdbx_struct_sheet_hbond.range_2_label_atom_id / _pdbx_struct_sheet_hbond.range_2_label_comp_id / _pdbx_struct_sheet_hbond.range_2_label_seq_id / _pdbx_struct_sheet_hbond.sheet_id / _pdbx_validate_chiral.auth_seq_id / _struct_conf.beg_auth_comp_id / _struct_conf.beg_auth_seq_id / _struct_conf.beg_label_comp_id / _struct_conf.beg_label_seq_id / _struct_conf.pdbx_PDB_helix_id / _struct_conf.pdbx_PDB_helix_length / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_seq_id / _struct_conn.ptnr2_symmetry / _struct_sheet.id / _struct_sheet_order.sheet_id / _struct_sheet_range.sheet_id / _struct_site.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 2.1Apr 24, 2019Group: Data collection / Source and taxonomy / Category: entity_src_gen / Item: _entity_src_gen.pdbx_host_org_cell_line
Revision 2.2May 8, 2019Group: Data collection / Experimental preparation / Category: exptl_crystal_grow / Item: _exptl_crystal_grow.method
Revision 3.0Jul 29, 2020Group: Atomic model / Data collection ...Atomic model / Data collection / Derived calculations / Other / Structure summary
Category: atom_site / chem_comp ...atom_site / chem_comp / entity / pdbx_branch_scheme / pdbx_chem_comp_identifier / pdbx_database_status / pdbx_entity_branch / pdbx_entity_branch_descriptor / pdbx_entity_branch_link / pdbx_entity_branch_list / pdbx_entity_nonpoly / pdbx_nonpoly_scheme / pdbx_struct_assembly_gen / struct_asym / struct_conn / struct_site / struct_site_gen
Item: _atom_site.B_iso_or_equiv / _atom_site.Cartn_x ..._atom_site.B_iso_or_equiv / _atom_site.Cartn_x / _atom_site.Cartn_y / _atom_site.Cartn_z / _atom_site.auth_asym_id / _atom_site.auth_seq_id / _atom_site.label_asym_id / _atom_site.label_entity_id / _chem_comp.name / _chem_comp.type / _pdbx_database_status.status_code_sf / _pdbx_entity_nonpoly.entity_id / _pdbx_entity_nonpoly.name / _pdbx_struct_assembly_gen.asym_id_list / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_role / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_seq_id / _struct_conn.ptnr2_symmetry
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 3.1Dec 20, 2023Group: Data collection / Database references ...Data collection / Database references / Refinement description / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _chem_comp.pdbx_synonyms / _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 3.2Oct 23, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 3
C: VASCULAR ENDOTHELIAL GROWTH FACTOR C
hetero molecules


Theoretical massNumber of molelcules
Total (without water)38,7607
Polymers37,4512
Non-polymers1,3095
Water00
1
A: VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 3
C: VASCULAR ENDOTHELIAL GROWTH FACTOR C
hetero molecules

A: VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 3
C: VASCULAR ENDOTHELIAL GROWTH FACTOR C
hetero molecules


Theoretical massNumber of molelcules
Total (without water)77,52114
Polymers74,9024
Non-polymers2,61810
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_455-x-1,-y,z1
Buried area4080 Å2
ΔGint-35.2 kcal/mol
Surface area38280 Å2
MethodPISA
Unit cell
Length a, b, c (Å)166.660, 166.660, 166.660
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number197
Space group name H-MI23

-
Components

#1: Protein VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR 3 / VEGFR-3 / FMS-LIKE TYROSINE KINASE 4 / FLT-4 / TYROSINE-PROTEIN KINASE RECEPTOR FLT4 / VEGFR-3


Mass: 23856.611 Da / Num. of mol.: 1 / Fragment: LIGAND-BINDING DOMAINS D1-2, RESIDUES 23-229
Source method: isolated from a genetically manipulated source
Details: COVALENT N-GLYCOSYLATION IN ASN33, ASN104 AND ASN166
Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PFASTBAC1 / Cell line (production host): Sf21 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm)
References: UniProt: P35916, receptor protein-tyrosine kinase
#2: Protein VASCULAR ENDOTHELIAL GROWTH FACTOR C / VEGF-C / FLT4 LIGAND / FLT4-L / VASCULAR ENDOTHELIAL GROWTH FACTOR-RELATED PROTEIN / VRP / VEGF-C


Mass: 13594.500 Da / Num. of mol.: 1 / Fragment: VEGF HOMOLOGY DOMAIN, RESIDUES 103-215 / Mutation: YES
Source method: isolated from a genetically manipulated source
Details: COVALENT N-GLYCOSYLATION IN ASN175 AND ASN205 / Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PFASTBAC1 / Cell line (production host): Sf21 / Production host: SPODOPTERA FRUGIPERDA (fall armyworm) / References: UniProt: P49767
#3: Polysaccharide 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-Glycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}}LINUCSPDB-CARE
#4: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 5.2 Å3/Da / Density % sol: 72 % / Description: NONE
Crystal growMethod: vapor diffusion, sitting drop / pH: 9
Details: SITTING DROPS AT ROOM TEMPERATURE OVER A RESERVOIR SOLUTION OF 0.1 M BIS-TRIS BUFFER AT PH 8.5-9.5 AND 1.0-1.5 M AMMONIUM SULPHATE.

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Oct 8, 2011
RadiationMonochromator: LN2 COOLED FIXED-EXIT SI(111) MONOCHROMATOR / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 4.2→30 Å / Num. obs: 5765 / % possible obs: 99.6 % / Observed criterion σ(I): -3 / Redundancy: 9.9 % / Rmerge(I) obs: 0.05 / Net I/σ(I): 20.9
Reflection shellResolution: 4.2→4.4 Å / Redundancy: 10.5 % / Rmerge(I) obs: 1.49 / Mean I/σ(I) obs: 2.1 / % possible all: 100

-
Processing

Software
NameClassification
XDSdata reduction
XDSdata scaling
autoSHARPphasing
MOLREPphasing
PHENIXrefinement
RefinementMethod to determine structure: MIRAS
Starting model: PDB ENTRIES 2X1X, 1FLT AND 2E9W

2x1x

1flt

2e9w


Resolution: 4.201→19.92 Å / SU ML: 0.96 / σ(F): 2 / Phase error: 52.28 / Stereochemistry target values: MLHL
Details: RESIDUES 103-114 AND 213-215 IN VEGF-C AND RESIDUES 23-27, 77-89, 114-123, 211-212 AND 225-229 IN VEGFR-3 ARE DISORDERED. ATOMS OF DISORDERED SIDECHAINS WERE OMITTED FROM THE FINAL MODEL.
RfactorNum. reflection% reflection
Rfree0.3718 572 10 %
Rwork0.3341 --
obs0.338 5721 100 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 135.9 Å2
Refinement stepCycle: LAST / Resolution: 4.201→19.92 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1792 0 84 0 1876
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0041924
X-RAY DIFFRACTIONf_angle_d1.0322651
X-RAY DIFFRACTIONf_dihedral_angle_d15.257615
X-RAY DIFFRACTIONf_chiral_restr0.061337
X-RAY DIFFRACTIONf_plane_restr0.006339
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
4.2008-4.61870.43791420.39531275X-RAY DIFFRACTION100
4.6187-5.27620.4771410.42121275X-RAY DIFFRACTION100
5.2762-6.60690.45261430.44651280X-RAY DIFFRACTION100
6.6069-19.91990.32391460.27891319X-RAY DIFFRACTION100
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
10.1414-0.27920.14140.5692-0.25820.16460.1784-0.1823-0.27640.18890.29240.17950.09550.17960.14171.1568-0.4292-0.0070.9691-0.28660.8004-91.86440.2163-14.9626
20.04090.05820.03560.04660.04250.0149-0.0916-0.08860.0569-0.0048-0.0077-0.1687-0.10480.0191-0.15940.796-0.8554-0.36020.2624-0.59380.4524-72.051532.4435-21.6582
30.04520.0392-0.05010.0406-0.04190.04930.16950.16910.09790.02150.3504-0.2343-0.08480.01090.14281.4476-0.85620.01240.7205-0.18391.3619-52.806553.2412-18.6545
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1CHAIN C AND ((RESSEQ 115:213))
2X-RAY DIFFRACTION2CHAIN A AND ((RESSEQ 134:224))
3X-RAY DIFFRACTION3CHAIN A AND ((RESSEQ 28:133))

+
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