+
Open data
-
Basic information
Entry | Database: PDB / ID: 7ab8 | ||||||
---|---|---|---|---|---|---|---|
Title | Crystal structure of a GDNF-GFRalpha1 complex | ||||||
![]() |
| ||||||
![]() | SIGNALING PROTEIN / VERTEBRATE DEVELOPMENT / PART OF THE RET-GFL-GFRA COMPLEX / NEUROTROPHIC FACTOR | ||||||
Function / homology | ![]() diencephalon development / positive regulation of ureteric bud formation / postganglionic parasympathetic fiber development / positive regulation of monooxygenase activity / regulation of dopaminergic neuron differentiation / glial cell-derived neurotrophic factor receptor binding / glial cell-derived neurotrophic factor receptor signaling pathway / regulation of morphogenesis of a branching structure / regulation of dopamine uptake involved in synaptic transmission / enteric nervous system development ...diencephalon development / positive regulation of ureteric bud formation / postganglionic parasympathetic fiber development / positive regulation of monooxygenase activity / regulation of dopaminergic neuron differentiation / glial cell-derived neurotrophic factor receptor binding / glial cell-derived neurotrophic factor receptor signaling pathway / regulation of morphogenesis of a branching structure / regulation of dopamine uptake involved in synaptic transmission / enteric nervous system development / peristalsis / positive regulation of branching involved in ureteric bud morphogenesis / sympathetic nervous system development / peripheral nervous system development / metanephros development / mRNA stabilization / neural crest cell migration / branching involved in ureteric bud morphogenesis / MAP kinase kinase kinase activity / growth factor activity / receptor tyrosine kinase binding / neuron projection development / nervous system development / signaling receptor activity / protein-containing complex assembly / negative regulation of neuron apoptotic process / receptor complex / external side of plasma membrane / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular region Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Adams, S.E. / Earl, C.P. / Purkiss, A.G. / McDonald, N.Q. | ||||||
Funding support | ![]()
| ||||||
![]() | ![]() Title: A two-site flexible clamp mechanism for RET-GDNF-GFRα1 assembly reveals both conformational adaptation and strict geometric spacing. Authors: Sarah E Adams / Andrew G Purkiss / Phillip P Knowles / Andrea Nans / David C Briggs / Annabel Borg / Christopher P Earl / Kerry M Goodman / Agata Nawrotek / Aaron J Borg / Pauline B McIntosh ...Authors: Sarah E Adams / Andrew G Purkiss / Phillip P Knowles / Andrea Nans / David C Briggs / Annabel Borg / Christopher P Earl / Kerry M Goodman / Agata Nawrotek / Aaron J Borg / Pauline B McIntosh / Francesca M Houghton / Svend Kjær / Neil Q McDonald / ![]() Abstract: RET receptor tyrosine kinase plays vital developmental and neuroprotective roles in metazoans. GDNF family ligands (GFLs) when bound to cognate GFRα co-receptors recognize and activate RET ...RET receptor tyrosine kinase plays vital developmental and neuroprotective roles in metazoans. GDNF family ligands (GFLs) when bound to cognate GFRα co-receptors recognize and activate RET stimulating its cytoplasmic kinase function. The principles for RET ligand-co-receptor recognition are incompletely understood. Here, we report a crystal structure of the cadherin-like module (CLD1-4) from zebrafish RET revealing interdomain flexibility between CLD2 and CLD3. Comparison with a cryo-electron microscopy structure of a ligand-engaged zebrafish RET-GDNF-GFRα1a complex indicates conformational changes within a clade-specific CLD3 loop adjacent to the co-receptor. Our observations indicate that RET is a molecular clamp with a flexible calcium-dependent arm that adapts to different GFRα co-receptors, while its rigid arm recognizes a GFL dimer to align both membrane-proximal cysteine-rich domains. We also visualize linear arrays of RET-GDNF-GFRα1a suggesting that a conserved contact stabilizes higher-order species. Our study reveals that ligand-co-receptor recognition by RET involves both receptor plasticity and strict spacing of receptor dimers by GFL ligands. | ||||||
History |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 145.6 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 106.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 769.5 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 771.6 KB | Display | |
Data in XML | ![]() | 16.7 KB | Display | |
Data in CIF | ![]() | 23.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7amkC ![]() 7amlC ![]() 3fubS S: Starting model for refinement C: citing same article ( |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
| ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | ![]()
| ||||||||||||
Unit cell |
|
-
Components
-Protein , 2 types, 2 molecules AB
#1: Protein | Mass: 23366.529 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
---|---|
#2: Protein | Mass: 11281.832 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
-Sugars , 1 types, 1 molecules
#3: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source |
---|
-Non-polymers , 3 types, 229 molecules ![](data/chem/img/EDO.gif)
![](data/chem/img/PEG.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/PEG.gif)
![](data/chem/img/HOH.gif)
#4: Chemical | ChemComp-EDO / #5: Chemical | ChemComp-PEG / #6: Water | ChemComp-HOH / | |
---|
-Details
Has ligand of interest | N |
---|
-Experimental details
-Experiment
Experiment | Method: ![]() |
---|
-
Sample preparation
Crystal | Density Matthews: 2.61 Å3/Da / Density % sol: 52.94 % |
---|---|
Crystal grow | Temperature: 295 K / Method: vapor diffusion / pH: 8 / Details: Tris, PEG 20K, MeCN, NaCl |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: ![]() ![]() ![]() |
Detector | Type: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: Jun 26, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.9795 Å / Relative weight: 1 |
Reflection | Resolution: 2.2→50.78 Å / Num. obs: 25823 / % possible obs: 91.93 % / Redundancy: 2 % / Biso Wilson estimate: 20.87 Å2 / CC1/2: 0.997 / CC star: 0.999 / Rmerge(I) obs: 0.05616 / Rpim(I) all: 0.05616 / Rrim(I) all: 0.07942 / Net I/σ(I): 12.3 |
Reflection shell | Resolution: 2.2→2.279 Å / Redundancy: 2 % / Rmerge(I) obs: 0.3711 / Mean I/σ(I) obs: 3.15 / Num. unique obs: 1368 / CC1/2: 0.797 / CC star: 0.942 / Rpim(I) all: 0.3711 / Rrim(I) all: 0.5247 / % possible all: 53.94 |
-
Processing
Software |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: ![]() Starting model: 3FUB Resolution: 2.2→50.76 Å / SU ML: 0.2217 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 22.6954 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 30.19 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.2→50.76 Å
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell |
|