[English] 日本語
Yorodumi
- PDB-6gl7: Neurturin-GFRa2-RET extracellular complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6gl7
TitleNeurturin-GFRa2-RET extracellular complex
Components
  • GDNF family receptor alpha-2
  • Neurturin
  • Proto-oncogene tyrosine-protein kinase receptor Ret
KeywordsSIGNALING PROTEIN / Neurotrophic signalling / Receptor tyrosine kinase / GDNF family of ligands
Function / homology
Function and homology information


RET signaling / RAF/MAP kinase cascade / NCAM1 interactions / glial cell-derived neurotrophic factor receptor activity / embryonic epithelial tube formation / glial cell-derived neurotrophic factor receptor signaling pathway / lymphocyte migration into lymphoid organs / positive regulation of metanephric glomerulus development / Peyer's patch morphogenesis / posterior midgut development ...RET signaling / RAF/MAP kinase cascade / NCAM1 interactions / glial cell-derived neurotrophic factor receptor activity / embryonic epithelial tube formation / glial cell-derived neurotrophic factor receptor signaling pathway / lymphocyte migration into lymphoid organs / positive regulation of metanephric glomerulus development / Peyer's patch morphogenesis / posterior midgut development / enteric nervous system development / ureter maturation / membrane protein proteolysis / positive regulation of peptidyl-serine phosphorylation of STAT protein / innervation / plasma membrane protein complex / neuron cell-cell adhesion / nerve development / positive regulation of neuron maturation / neuron maturation / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / negative regulation of protein autophosphorylation / positive regulation of cell adhesion mediated by integrin / neurogenesis / positive regulation of cell size / response to pain / neural crest cell migration / regulation of axonogenesis / ureteric bud development / homophilic cell adhesion via plasma membrane adhesion molecules / regulation of cell adhesion / retina development in camera-type eye / extrinsic component of membrane / anchored component of membrane / cellular response to retinoic acid / positive regulation of neuron projection development / receptor protein-tyrosine kinase / transmembrane receptor protein tyrosine kinase activity / neuron projection development / activation of cysteine-type endopeptidase activity involved in apoptotic process / nervous system development / growth factor activity / axon guidance / positive regulation of MAPK cascade / transmembrane receptor protein tyrosine kinase signaling pathway / response to drug / signaling receptor activity / protein tyrosine kinase activity / activation of MAPK activity / receptor complex / early endosome / endosome membrane / MAPK cascade / cell differentiation / positive regulation of cell migration / positive regulation of protein kinase B signaling / membrane raft / external side of plasma membrane / intracellular membrane-bounded organelle / axon / dendrite / neuronal cell body / signaling receptor binding / protein phosphorylation / positive regulation of transcription, DNA-templated / calcium ion binding / integral component of plasma membrane / signal transduction / extracellular region / ATP binding / plasma membrane / cytosol
Glial cell line-derived neurotrophic factor receptor / Glial cell line-derived neurotrophic factor receptor, alpha 1/2 / RET cadherin-like domain 4 / Ret, cadherin like domain 1 / Glial cell line-derived neurotrophic factor receptor alpha 2 / GDNF receptor alpha / Cystine-knot cytokine / Tyrosine-protein kinase, catalytic domain / Protein kinase, ATP binding site / Tyrosine-protein kinase, Ret receptor ...Glial cell line-derived neurotrophic factor receptor / Glial cell line-derived neurotrophic factor receptor, alpha 1/2 / RET cadherin-like domain 4 / Ret, cadherin like domain 1 / Glial cell line-derived neurotrophic factor receptor alpha 2 / GDNF receptor alpha / Cystine-knot cytokine / Tyrosine-protein kinase, catalytic domain / Protein kinase, ATP binding site / Tyrosine-protein kinase, Ret receptor / Cadherin domain / GDNF/GAS1 / Cadherin-like superfamily / Protein kinase-like domain superfamily / Tyrosine-protein kinase, active site / Protein kinase domain / Serine-threonine/tyrosine-protein kinase, catalytic domain / Transforming growth factor-beta, C-terminal / Cadherin-like / Transforming growth factor beta like domain / Tyrosine-protein kinase receptor Ret, cadherin like domain 3 / GDNF/GAS1 domain / RET Cadherin like domain 1 / TGF-beta family profile. / Cadherins domain profile. / Protein kinase domain profile. / Tyrosine protein kinases specific active-site signature. / Protein kinases ATP-binding region signature. / RET Cadherin like domain 3 / RET Cadherin like domain 4 / Protein tyrosine kinase
GDNF family receptor alpha-2 / Proto-oncogene tyrosine-protein kinase receptor Ret / Neurturin
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 6.3 Å
AuthorsBigalke, J.M. / Aibara, S. / Sandmark, J. / Amunts, A.
Funding support Sweden, 5items
OrganizationGrant numberCountry
FFL15:0325 Sweden
Knut and Alice Wallenberg Foundation Sweden
M44/16 Sweden
Swedish Research CouncilNT_2015-04107 Sweden
CAN 2017/1041 Sweden
CitationJournal: 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.
Validation Report
SummaryFull reportAbout validation report
History
DepositionMay 23, 2018Deposition site: PDBE / Processing site: PDBE
Revision 1.0Aug 14, 2019Provider: repository / Type: Initial release
Revision 1.1Aug 21, 2019Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-0026
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
B: Neurturin
D: GDNF family receptor alpha-2
A: Neurturin
C: GDNF family receptor alpha-2
F: Proto-oncogene tyrosine-protein kinase receptor Ret
E: Proto-oncogene tyrosine-protein kinase receptor Ret


Theoretical massNumber of molelcules
Total (without water)255,9876
Polymers255,9876
Non-polymers00
Water0
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration, surface plasmon resonance
  • Download structure data
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area10460 Å2
ΔGint-5 kcal/mol
Surface area82960 Å2
MethodPISA

-
Components

#1: Protein/peptide Neurturin


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/peptide GDNF family receptor alpha-2 / GFR-alpha-2 / GDNF receptor beta / GDNFR-beta / Neurturin receptor alpha / NTNR-alpha / RET ligand 2 / TGF-beta-related neurotrophic factor receptor 2


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/peptide Proto-oncogene tyrosine-protein kinase receptor Ret / Cadherin family member 12 / Proto-oncogene c-Ret


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

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

Component

Type: COMPLEX

IDNameEntity IDParent-IDSource
1Neurturin-GFRa2-RET extracellular complex1, 2, 30MULTIPLE SOURCES
2Neurturin11RECOMBINANT
3GDNF family receptor alpha-221RECOMBINANT
4Proto-oncogene tyrosine-protein kinase receptor Ret31RECOMBINANT
Molecular weightValue: 0.254 MDa / Experimental value: NO
Source (natural)

Ncbi tax-ID: 9606 / Organism: Homo sapiens (human)

IDEntity assembly-ID
12
23
34
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-ID
12Escherichia coli (E. coli)562
23Cricetulus griseus (Chinese hamster)10029
34Cricetulus griseus (Chinese hamster)10029
Buffer solutionpH: 8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy
Image recordingElectron dose: 38 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 QUANTUM (4k x 4k)

-
Processing

EM software
IDNameCategory
7UCSF Chimeramodel fitting
8Cootmodel fitting
10PHENIXmodel refinement
11RosettaEMmodel refinement
12Cootmodel refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
SymmetryPoint symmetry: C2 (2 fold cyclic)
3D reconstructionResolution: 6.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 186903 / Symmetry type: POINT
Atomic model buildingB value: 220 / Protocol: FLEXIBLE FIT / Space: REAL

+
About Yorodumi

-
News

-
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. (see PDBe EMDB page)
  • 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 at PDBe / 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. See below links for details.
  • 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

+
Jun 16, 2017. Omokage search with filter

Omokage search with filter

  • Result of Omokage search can be filtered by keywords and the database types

Related info.: Omokage search

+
Sep 15, 2016. EM Navigator & Yorodumi renewed

EM Navigator & Yorodumi renewed

  • New versions of EM Navigator and Yorodumi started

Related info.: Changes in new EM Navigator and Yorodumi

+
Aug 31, 2016. New EM Navigator & Yorodumi

New EM Navigator & Yorodumi

  • In 15th Sep 2016, the development versions of EM Navigator and Yorodumi will replace the official versions.
  • Current version will continue as 'legacy version' for some time.

Related info.: Changes in new EM Navigator and Yorodumi / EM Navigator / Yorodumi

Read more

-
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.

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