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- PDB-3fub: Crystal structure of GDNF-GFRalpha1 complex -

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Basic information

Entry
Database: PDB / ID: 3fub
TitleCrystal structure of GDNF-GFRalpha1 complex
Components
  • GDNF family receptor alpha-1GFRα
  • Glial cell line-derived neurotrophic factor
KeywordsHORMONE / GFRALPHA1 / ALL ALPHA GDNF / CYSTINE KNOT / Cell membrane / Glycoprotein / GPI-anchor / Lipoprotein / Membrane / Receptor / Cleavage on pair of basic residues / Disease mutation / Growth factor / Hirschsprung disease / Secreted
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 / positive regulation of branching involved in ureteric bud morphogenesis / peristalsis / positive regulation of dopamine secretion / sympathetic nervous system development / peripheral nervous system development / organ induction / plasma membrane protein complex / regulation of stem cell differentiation / 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 / receptor tyrosine kinase binding / neuron differentiation / 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 / axon / external side of plasma membrane / 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
Glial cell line-derived neurotrophic factor / GDNF family receptor alpha-1
Similarity search - Component
Biological speciesHomo sapiens (human)
Rattus norvegicus (Norway rat)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.35 Å
AuthorsParkash, V. / Goldman, A.
CitationJournal: Acta Crystallogr.,Sect.F / Year: 2009
Title: Comparison of GFL-GFRalpha complexes: further evidence relating GFL bend angle to RET signalling
Authors: Parkash, V. / Goldman, A.
History
DepositionJan 14, 2009Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 2, 2009Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Non-polymer description / Version format compliance
Revision 1.2Jan 24, 2018Group: Structure summary / Category: audit_author / Item: _audit_author.name
Revision 2.0Jul 29, 2020Group: Atomic model / Data collection ...Atomic model / Data collection / Derived calculations / Structure summary
Category: atom_site / chem_comp ...atom_site / chem_comp / entity / pdbx_branch_scheme / pdbx_chem_comp_identifier / 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_atom_id / _atom_site.auth_comp_id / _atom_site.auth_seq_id / _atom_site.label_asym_id / _atom_site.label_atom_id / _atom_site.label_comp_id / _atom_site.label_entity_id / _atom_site.type_symbol / _chem_comp.name / _chem_comp.type / _pdbx_entity_nonpoly.entity_id / _pdbx_entity_nonpoly.name / _pdbx_struct_assembly_gen.asym_id_list / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.pdbx_role / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id
Description: Carbohydrate remediation / Provider: repository / Type: Remediation
Revision 2.1Sep 6, 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
C: GDNF family receptor alpha-1
D: Glial cell line-derived neurotrophic factor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)93,34710
Polymers92,4194
Non-polymers9286
Water3,009167
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)93,23412
Polymers92,4194
Non-polymers8158
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_655-x+1,y,-z1
Buried area8130 Å2
ΔGint-10 kcal/mol
Surface area29630 Å2
MethodPISA
2
C: GDNF family receptor alpha-1
D: Glial cell line-derived neurotrophic factor
hetero molecules

C: GDNF family receptor alpha-1
D: Glial cell line-derived neurotrophic factor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)93,4608
Polymers92,4194
Non-polymers1,0414
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_756-x+2,y,-z+11
Buried area7450 Å2
ΔGint-39 kcal/mol
Surface area32010 Å2
MethodPISA
Unit cell
Length a, b, c (Å)45.200, 84.100, 179.200
Angle α, β, γ (deg.)90.00, 96.10, 90.00
Int Tables number5
Space group name H-MC121

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Components

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Protein , 2 types, 4 molecules ACBD

#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: 31113.260 Da / Num. of mol.: 2 / Fragment: sequence database residues 145-425 / Source method: isolated from a natural source / Source: (natural) Rattus norvegicus (Norway rat) / References: UniProt: Q62997
#2: Protein Glial cell line-derived neurotrophic factor / / Astrocyte-derived trophic factor / ATF / hGDNF


Mass: 15096.242 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GDNF / Plasmid: PFASTBAC / Production host: Spodoptera Frugiperda (fall armyworm) / References: UniProt: P39905

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Sugars , 2 types, 2 molecules

#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
#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 , 3 types, 171 molecules

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


Mass: 62.068 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C2H6O2
#6: Chemical ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#7: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 167 / Source method: isolated from a natural source / Formula: H2O

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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: 2.55 Å3/Da / Density % sol: 51.86 %
Crystal growTemperature: 293 K / Method: vapor diffusion / pH: 6
Details: 15% PEG4000, 0.15 M (NH4)2SO4, 0.1 M MES buffer pH 6, Vapor diffusion, temperature 293K

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Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID14-1 / Wavelength: 0.933 Å
DetectorType: ADSC QUANTUM 210 / Detector: CCD / Date: Jun 27, 2008
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.933 Å / Relative weight: 1
ReflectionResolution: 2.35→42 Å / Num. all: 31756 / Num. obs: 30497 / % possible obs: 97 % / Observed criterion σ(F): 1 / Observed criterion σ(I): -3 / Redundancy: 3.8 % / Rsym value: 0.09
Reflection shellResolution: 2.35→2.45 Å / Redundancy: 3.1 % / Mean I/σ(I) obs: 2.95 / Rsym value: 0.43 / % possible all: 91.3

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Phasing

PhasingMethod: molecular replacement

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Processing

Software
NameVersionClassificationNB
XSCALEdata scaling
PHASERphasing
REFMACrefinement
PDB_EXTRACT3.006data extraction
MxCuBEdata collection
XDSdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entry 2V5E
Resolution: 2.35→20 Å / Cor.coef. Fo:Fc: 0.888 / Cor.coef. Fo:Fc free: 0.841 / Occupancy max: 1 / Occupancy min: 1 / SU B: 9.56 / SU ML: 0.23 / Isotropic thermal model: Isotropic / Cross valid method: THROUGHOUT / ESU R: 0.466 / ESU R Free: 0.292 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.28021 1358 5 %RANDOM
Rwork0.22554 ---
obs0.22834 25681 97.05 %-
all-31756 --
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso mean: 24.308 Å2
Baniso -1Baniso -2Baniso -3
1--0.04 Å20 Å20.19 Å2
2---1.31 Å20 Å2
3---1.4 Å2
Refinement stepCycle: LAST / Resolution: 2.35→20 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4561 0 59 167 4787
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.0214720
X-RAY DIFFRACTIONr_bond_other_d
X-RAY DIFFRACTIONr_angle_refined_deg1.0911.9686385
X-RAY DIFFRACTIONr_angle_other_deg
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.4935588
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.86923.645214
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.91815787
X-RAY DIFFRACTIONr_dihedral_angle_4_deg14.7371538
X-RAY DIFFRACTIONr_chiral_restr0.0770.2715
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.0213543
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_it0.8391.52950
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it1.56124722
X-RAY DIFFRACTIONr_scbond_it2.30131770
X-RAY DIFFRACTIONr_scangle_it3.6554.51663
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% reflection
Rfree0.339 82 -
Rwork0.256 1773 -
obs--90.89 %

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