+Open data
-Basic information
Entry | Database: PDB / ID: 6gl7 | ||||||||||||||||||
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Title | Neurturin-GFRa2-RET extracellular complex | ||||||||||||||||||
Components |
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Keywords | SIGNALING PROTEIN / Neurotrophic signalling / Receptor tyrosine kinase / GDNF family of ligands | ||||||||||||||||||
Function / homology | Function and homology information glial cell-derived neurotrophic factor receptor activity / glial cell-derived neurotrophic factor receptor binding / GDF15-GFRAL signaling pathway / Peyer's patch morphogenesis / positive regulation of metanephric glomerulus development / posterior midgut development / ureter maturation / embryonic epithelial tube formation / glial cell-derived neurotrophic factor receptor signaling pathway / lymphocyte migration into lymphoid organs ...glial cell-derived neurotrophic factor receptor activity / glial cell-derived neurotrophic factor receptor binding / GDF15-GFRAL signaling pathway / Peyer's patch morphogenesis / positive regulation of metanephric glomerulus development / posterior midgut development / ureter maturation / embryonic epithelial tube formation / glial cell-derived neurotrophic factor receptor signaling pathway / lymphocyte migration into lymphoid organs / membrane protein proteolysis / positive regulation of peptidyl-serine phosphorylation of STAT protein / Formation of the ureteric bud / positive regulation of neuron maturation / neuron cell-cell adhesion / Formation of the nephric duct / enteric nervous system development / nerve development / innervation / plasma membrane protein complex / neuron maturation / heparan sulfate binding / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / NCAM1 interactions / positive regulation of cell adhesion mediated by integrin / neural crest cell migration / ureteric bud development / regulation of axonogenesis / extrinsic component of membrane / response to pain / homophilic cell adhesion via plasma membrane adhesion molecules / positive regulation of cell size / RET signaling / transmembrane receptor protein tyrosine kinase activity / regulation of cell adhesion / cellular response to retinoic acid / cell surface receptor protein tyrosine kinase signaling pathway / NPAS4 regulates expression of target genes / axon guidance / receptor protein-tyrosine kinase / growth factor activity / receptor tyrosine kinase binding / activation of cysteine-type endopeptidase activity involved in apoptotic process / positive regulation of neuron projection development / MAPK cascade / neuron projection development / retina development in camera-type eye / signaling receptor activity / nervous system development / RAF/MAP kinase cascade / protein tyrosine kinase activity / receptor complex / positive regulation of MAPK cascade / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / endosome membrane / early endosome / positive regulation of cell migration / response to xenobiotic stimulus / protein phosphorylation / external side of plasma membrane / axon / signaling receptor binding / neuronal cell body / dendrite / calcium ion binding / positive regulation of gene expression / positive regulation of DNA-templated transcription / signal transduction / extracellular space / extracellular region / ATP binding / plasma membrane Similarity search - Function | ||||||||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 6.3 Å | ||||||||||||||||||
Authors | Bigalke, J.M. / Aibara, S. / Sandmark, J. / Amunts, A. | ||||||||||||||||||
Funding support | Sweden, 5items
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Citation | Journal: Sci Adv / Year: 2019 Title: Cryo-EM structure of the activated RET signaling complex reveals the importance of its cysteine-rich domain. Authors: Janna M Bigalke / Shintaro Aibara / Robert Roth / Göran Dahl / Euan Gordon / Sarah Dorbéus / A Amunts / Jenny Sandmark / Abstract: Signaling through the receptor tyrosine kinase RET is essential during normal development. Both gain- and loss-of-function mutations are involved in a variety of diseases, yet the molecular details ...Signaling through the receptor tyrosine kinase RET is essential during normal development. Both gain- and loss-of-function mutations are involved in a variety of diseases, yet the molecular details of receptor activation have remained elusive. We have reconstituted the complete extracellular region of the RET signaling complex together with Neurturin (NRTN) and GFRα2 and determined its structure at 5.7-Å resolution by cryo-EM. The proteins form an assembly through RET-GFRα2 and RET-NRTN interfaces. Two key interaction points required for RET extracellular domain binding were observed: (i) the calcium-binding site in RET that contacts GFRα2 domain 3 and (ii) the RET cysteine-rich domain interaction with NRTN. The structure highlights the importance of the RET cysteine-rich domain and allows proposition of a model to explain how complex formation leads to RET receptor dimerization and its activation. This provides a framework for targeting RET activity and for further exploration of mechanisms underlying neurological diseases. | ||||||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6gl7.cif.gz | 563.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6gl7.ent.gz | 477.2 KB | Display | PDB format |
PDBx/mmJSON format | 6gl7.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6gl7_validation.pdf.gz | 955.4 KB | Display | wwPDB validaton report |
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Full document | 6gl7_full_validation.pdf.gz | 967.3 KB | Display | |
Data in XML | 6gl7_validation.xml.gz | 62.8 KB | Display | |
Data in CIF | 6gl7_validation.cif.gz | 92.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/gl/6gl7 ftp://data.pdbj.org/pub/pdb/validation_reports/gl/6gl7 | HTTPS FTP |
-Related structure data
Related structure data | 0026MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 11706.406 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: NRTN / Production host: Escherichia coli (E. coli) / References: UniProt: Q99748 #2: Protein | Mass: 47635.629 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GFRA2, GDNFRB, RETL2, TRNR2 / Production host: Cricetulus griseus (Chinese hamster) / References: UniProt: O00451 #3: Protein | Mass: 68651.352 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: RET, CDHF12, CDHR16, PTC, RET51 / Production host: Cricetulus griseus (Chinese hamster) References: UniProt: P07949, receptor protein-tyrosine kinase |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component |
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Molecular weight | Value: 0.254 MDa / Experimental value: NO | ||||||||||||||||||||||||||||||
Source (natural) |
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Source (recombinant) |
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Buffer solution | pH: 8 | ||||||||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 38 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 QUANTUM (4k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||
3D reconstruction | Resolution: 6.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 186903 / Symmetry type: POINT | ||||||||||||||||||
Atomic model building | B value: 220 / Protocol: FLEXIBLE FIT / Space: REAL |