4OVE

X-ray Crystal Structure of Mouse Netrin-1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.64 Å
  • R-Value Free: 0.288 
  • R-Value Work: 0.230 
  • R-Value Observed: 0.233 

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Ligand Structure Quality Assessment 


This is version 2.0 of the entry. See complete history


Literature

Structural Decoding of the Netrin-1/UNC5 Interaction and its Therapeutical Implications in Cancers.

Grandin, M.Meier, M.Delcros, J.G.Nikodemus, D.Reuten, R.Patel, T.R.Goldschneider, D.Orriss, G.Krahn, N.Boussouar, A.Abes, R.Dean, Y.Neves, D.Bernet, A.Depil, S.Schneiders, F.Poole, K.Dante, R.Koch, M.Mehlen, P.Stetefeld, J.

(2016) Cancer Cell 29: 173-185

  • DOI: https://doi.org/10.1016/j.ccell.2016.01.001
  • Primary Citation of Related Structures:  
    4OVE

  • PubMed Abstract: 

    Netrin-1 has been shown to be up-regulated in a fraction of human cancers as a mechanism to allow these tumors to escape the pro-apoptotic activity of some of its main dependence receptors, the UNC5 homologs (UNC5H). Here we identify the V-2 domain of netrin-1 to be important for its interaction with the Ig1/Ig2 domains of UNC5H2. We generate a humanized anti-netrin-1 antibody that disrupts the interaction between netrin-1 and UNC5H2 and triggers death of netrin-1-expressing tumor cells in vitro. We also present evidence that combining the anti-netrin-1 antibody with epidrugs such as decitabine could be effective in treating tumors showing no or modest netrin-1 expression. These results support that this antibody is a promising drug candidate.


  • Organizational Affiliation

    Apoptosis, Cancer and Development Laboratory, Equipe labellisée 'La Ligue', LabEx DEVweCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008 Lyon, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Netrin-1437Mus musculusMutation(s): 0 
Gene Names: Ntn1
UniProt
Find proteins for O09118 (Mus musculus)
Explore O09118 
Go to UniProtKB:  O09118
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO09118
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
B
5N-Glycosylation
Glycosylation Resources
GlyTouCan:  G22768VO
GlyCosmos:  G22768VO
GlyGen:  G22768VO
Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
C
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.64 Å
  • R-Value Free: 0.288 
  • R-Value Work: 0.230 
  • R-Value Observed: 0.233 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 69.754α = 90
b = 69.754β = 90
c = 334.802γ = 120
Software Package:
Software NamePurpose
HKL-2000data collection
SHARPphasing
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-02-25
    Type: Initial release
  • Version 1.1: 2015-03-11
    Changes: Derived calculations
  • Version 1.2: 2016-02-17
    Changes: Database references
  • Version 1.3: 2017-10-25
    Changes: Author supporting evidence
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Database references, Derived calculations, Structure summary