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- PDB-2v5e: The structure of the GDNF:Coreceptor complex: Insights into RET s... -

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Basic information

Entry
Database: PDB / ID: 2v5e
TitleThe structure of the GDNF:Coreceptor complex: Insights into RET signalling and heparin binding.
Components
  • GDNF FAMILY RECEPTOR ALPHA-1GFRα
  • GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTOR
KeywordsRECEPTOR/GLYCOPROTEIN COMPLEX / RECEPTOR-GLYCOPROTEIN COMPLEX / ALTERNATIVE SPLICING / CELL MEMBRANE / GROWTH FACTOR / LIGAND-CORECEPTOR / GPI-ANCHOR / LIPOPROTEIN / POLYMORPHISM / GLYCOPROTEIN / MEMBRANE / RECEPTOR / SECRETED / GFRALPHA1 / CLEAVAGE ON PAIR OF BASIC RESIDUES / RECEPTOR-GLYCOPROTEIN COMPLEX complex
Function / homology
Function and homology information


chemoattractant activity involved in axon guidance / postsynaptic membrane organization / mesenchymal to epithelial transition involved in metanephros morphogenesis / dorsal spinal cord development / positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis / ureteric bud formation / positive regulation of ureteric bud formation / regulation of semaphorin-plexin signaling pathway / postganglionic parasympathetic fiber development / positive regulation of monooxygenase activity ...chemoattractant activity involved in axon guidance / postsynaptic membrane organization / mesenchymal to epithelial transition involved in metanephros morphogenesis / dorsal spinal cord development / positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis / ureteric bud formation / positive regulation of ureteric bud formation / regulation of semaphorin-plexin signaling pathway / postganglionic parasympathetic fiber development / positive regulation of monooxygenase activity / glial cell-derived neurotrophic factor receptor binding / RET signaling / regulation of morphogenesis of a branching structure / neurotrophin receptor activity / regulation of dopamine uptake involved in synaptic transmission / enteric nervous system development / peristalsis / positive regulation of dopamine secretion / positive regulation of branching involved in ureteric bud morphogenesis / sympathetic nervous system development / peripheral nervous system development / organ induction / regulation of stem cell differentiation / plasma membrane protein complex / mRNA stabilization / commissural neuron axon guidance / metanephros development / NCAM1 interactions / RAF/MAP kinase cascade / neural crest cell migration / branching involved in ureteric bud morphogenesis / RET signaling / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / embryonic organ development / multivesicular body / adult locomotory behavior / kidney development / positive regulation of cell differentiation / growth factor activity / neuron differentiation / receptor tyrosine kinase binding / neuron projection development / male gonad development / positive regulation of peptidyl-tyrosine phosphorylation / cell migration / integrin binding / signaling receptor activity / nervous system development / RAF/MAP kinase cascade / regulation of gene expression / negative regulation of neuron apoptotic process / receptor complex / external side of plasma membrane / axon / signaling receptor binding / neuronal cell body / positive regulation of cell population proliferation / negative regulation of apoptotic process / Golgi apparatus / signal transduction / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular region / plasma membrane
Similarity search - Function
: / Glial cell line-derived neurotrophic factor receptor, alpha 1 / Glial cell line-derived neurotrophic factor / Glial cell line-derived neurotrophic factor receptor, alpha 1/2 / Glial cell line-derived neurotrophic factor receptor / GDNF receptor alpha / Glial cell line-derived neurotrophic factor family / GDNF/GAS1 / GDNF/GAS1 domain / GDNF/GAS1 domain ...: / Glial cell line-derived neurotrophic factor receptor, alpha 1 / Glial cell line-derived neurotrophic factor / Glial cell line-derived neurotrophic factor receptor, alpha 1/2 / Glial cell line-derived neurotrophic factor receptor / GDNF receptor alpha / Glial cell line-derived neurotrophic factor family / GDNF/GAS1 / GDNF/GAS1 domain / GDNF/GAS1 domain / Transforming growth factor-beta (TGF-beta) family / Transforming growth factor-beta, C-terminal / Transforming growth factor beta like domain / TGF-beta family profile. / Cystine Knot Cytokines, subunit B / Cystine-knot cytokines / Cystine-knot cytokine / Ribbon / Mainly Beta
Similarity search - Domain/homology
sucrose octasulfate / Glial cell line-derived neurotrophic factor / GDNF family receptor alpha-1
Similarity search - Component
Biological speciesRATTUS NORVEGICUS (Norway rat)
HOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.35 Å
AuthorsParkash, V. / Leppanen, V.-M. / Virtanen, H. / Jurvansuu, J.-M. / Bespalov, M.M. / Sidorova, Y.A. / Runeberg-Roos, P. / Saarma, M. / Goldman, A.
CitationJournal: J.Biol.Chem. / Year: 2008
Title: The Structure of the Glial Cell Line-Derived Neurotrophic Factor-Coreceptor Complex: Insights Into Ret Signaling and Heparin Binding.
Authors: Parkash, V. / Leppanen, V.-M. / Virtanen, H. / Jurvansuu, J.-M. / Bespalov, M.M. / Sidorova, Y.A. / Runeberg-Roos, P. / Saarma, M. / Goldman, A.
History
DepositionOct 3, 2008Deposition site: PDBE / Processing site: PDBE
Revision 1.0Oct 21, 2008Provider: repository / Type: Initial release
Revision 1.1Feb 5, 2014Group: Derived calculations / Non-polymer description ...Derived calculations / Non-polymer description / Other / Refinement description / Source and taxonomy / Structure summary / Version format compliance
Revision 2.0Jul 29, 2020Group: Atomic model / Data collection ...Atomic model / Data collection / Derived calculations / Non-polymer description / Other / Structure summary
Category: atom_site / chem_comp ...atom_site / chem_comp / entity / entity_name_com / 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_molecule_features / pdbx_nonpoly_scheme / struct_conn / struct_conn_type / 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_atom_id / _atom_site.auth_comp_id / _atom_site.auth_seq_id / _atom_site.label_atom_id / _atom_site.label_comp_id / _atom_site.type_symbol / _chem_comp.formula / _chem_comp.formula_weight / _chem_comp.id / _chem_comp.mon_nstd_flag / _chem_comp.name / _chem_comp.type / _entity.formula_weight / _entity.pdbx_description / _entity.type / _pdbx_database_status.status_code_sf / _struct_conn.conn_type_id / _struct_conn.id / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.pdbx_value_order / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_conn.ptnr2_symmetry
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 2.1Dec 13, 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

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: GDNF FAMILY RECEPTOR ALPHA-1
B: GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTOR
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,4218
Polymers33,9692
Non-polymers1,4526
Water4,017223
1
A: GDNF FAMILY RECEPTOR ALPHA-1
B: GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTOR
hetero molecules

A: GDNF FAMILY RECEPTOR ALPHA-1
B: GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTOR
hetero molecules


Theoretical massNumber of molelcules
Total (without water)70,84216
Polymers67,9374
Non-polymers2,90512
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_555-x,y,-z1
Buried area9120 Å2
ΔGint-26.7 kcal/mol
Surface area31120 Å2
MethodPISA
Unit cell
Length a, b, c (Å)58.900, 75.700, 105.500
Angle α, β, γ (deg.)90.00, 91.90, 90.00
Int Tables number5
Space group name H-MC121

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Components

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Protein , 2 types, 2 molecules AB

#1: Protein GDNF FAMILY RECEPTOR ALPHA-1 / GFRα / GFR-ALPHA-1 / GDNF RECEPTOR ALPHA / GDNFR-ALPHA / TGF-BETA-RELATED NEUROTROPHIC FACTOR RECEPTOR 1 / ...GFR-ALPHA-1 / GDNF RECEPTOR ALPHA / GDNFR-ALPHA / TGF-BETA-RELATED NEUROTROPHIC FACTOR RECEPTOR 1 / RET LIGAND 1


Mass: 22538.631 Da / Num. of mol.: 1 / Fragment: RESIDUES 150-349
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) RATTUS NORVEGICUS (Norway rat) / Plasmid: PFASTBAC / Cell line (production host): SF9
Production host: SPODOPTERA FRUGIPERDA; EXPRESSION_SYSTEM_COMMON_FALL ARMYWORM (fall armyworm)
References: UniProt: Q62997
#2: Protein GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTOR / / ASTROCYTE-DERIVED TROPHIC FACTOR / HGDNF / ATF


Mass: 11430.114 Da / Num. of mol.: 1 / Fragment: RESIDUES 111-211
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PFASTBAC / Cell line (production host): SF9
Production host: SPODOPTERA FRUGIPERDA; EXPRESSION_SYSTEM_COMMON_FALL ARMYWORM (fall armyworm)
References: UniProt: P39905

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Sugars , 2 types, 2 molecules

#3: Polysaccharide 1,3,4,6-tetra-O-sulfo-beta-D-fructofuranose-(2-1)-2,3,4,6-tetra-O-sulfonato-alpha-D-glucopyranose / sucrose octasulfate


Type: oligosaccharide, Oligosaccharide / Class: Substrate analog / Mass: 982.803 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: oligosaccharide with reducing-end-to-reducing-end glycosidic bond
References: sucrose octasulfate
DescriptorTypeProgram
WURCS=2.0/2,2,1/[ha122h-2b_2-5_1*OSO/3=O/3=O_3*OSO/3=O/3=O_4*OSO/3=O/3=O_6*OSO/3=O/3=O][a2122h-1a_1-5_2*OSO/3=O/3=O_3*OSO/3=O/3=O_4*OSO/3=O/3=O_6*OSO/3=O/3=O]/1-2/a2-b1WURCSPDB2Glycan 1.1.0
[][b-D-Fruf1SO33SO34SO36SO3]{[(2+1)][a-D-Glcp2SO33SO34SO36SO3]{}}LINUCSPDB-CARE
#5: 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 / N-Acetylglucosamine


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 1
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

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Non-polymers , 2 types, 227 molecules

#4: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL / Ethylene glycol


Mass: 62.068 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C2H6O2
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 223 / Source method: isolated from a natural source / Formula: H2O

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Details

Nonpolymer detailsN-ACETYLGLUCOSAMINE (NAG): THE N-GLYCAN IS LINKED TO GDNF CHAIN B RESIDUE N 49.
Sequence detailsTHE SEQUENCE NUMBERING OF THE MATURE GDNF EXCLUDES THE 77 RESIDUES OF THE PREPRO REGION FROM THE SEQUENCE.

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Experimental details

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Experiment

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

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Sample preparation

CrystalDensity Matthews: 2.35 Å3/Da / Density % sol: 48 % / Description: NONE
Crystal growpH: 7.5 / Details: 100MM HEPES PH7.5, 10% PEG-8K, 8% ETHYLENE GLYCOL

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Data collection

DiffractionMean temperature: 190 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID14-2 / Wavelength: 0.933
DetectorType: ADSC CCD / Detector: CCD / Date: Sep 6, 2006
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.933 Å / Relative weight: 1
ReflectionResolution: 2.35→20 Å / Num. obs: 19071 / % possible obs: 98.2 % / Observed criterion σ(I): -3 / Redundancy: 3.5 % / Biso Wilson estimate: 35 Å2 / Rmerge(I) obs: 0.08 / Net I/σ(I): 16
Reflection shellResolution: 2.35→2.45 Å / Redundancy: 2.5 % / Rmerge(I) obs: 0.29 / Mean I/σ(I) obs: 4.29 / % possible all: 87

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Processing

Software
NameVersionClassification
REFMAC5.4.0066refinement
XSCALEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRIES 1AGQ CHAIN A, 2GH0 CHAIN A
Resolution: 2.35→20 Å / Cor.coef. Fo:Fc: 0.94 / Cor.coef. Fo:Fc free: 0.909 / SU B: 5.822 / SU ML: 0.138 / Cross valid method: THROUGHOUT / ESU R: 0.265 / ESU R Free: 0.219 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. BECAUSE OF POOR ELECTRON DENSITY, FOLLOWING RESIDUES ATOMS WERE MISSING: ARG A 238 CG CD NE CZ NH1 NH2 LYS B 96 CG CD CE NZ
RfactorNum. reflection% reflectionSelection details
Rfree0.237 981 5.1 %RANDOM
Rwork0.184 ---
obs0.187 18089 98.4 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 26.91 Å2
Refinement stepCycle: LAST / Resolution: 2.35→20 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2348 0 85 223 2656
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0110.0222490
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.2061.9923374
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.4965301
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.56323.565115
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.81315425
X-RAY DIFFRACTIONr_dihedral_angle_4_deg14.8831522
X-RAY DIFFRACTIONr_chiral_restr0.0820.2378
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.0211822
X-RAY DIFFRACTIONr_gen_planes_other
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it2.12721501
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it3.48432412
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it2.3142989
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it3.4153961
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.35→2.41 Å / Total num. of bins used: 20 /
RfactorNum. reflection
Rfree0.336 51
Rwork0.247 1108

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