4CBZ

Notch ligand, Jagged-1, contains an N-terminal C2 domain


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.206 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Structural Analysis Uncovers Lipid-Binding Properties of Notch Ligands

Chilakuri, C.R.Sheppard, D.Ilagan, M.X.G.Holt, L.R.Abbott, F.Liang, S.Kopan, R.Handford, P.A.Lea, S.M.

(2013) Cell Rep 5: 861

  • DOI: https://doi.org/10.1016/j.celrep.2013.10.029
  • Primary Citation of Related Structures:  
    4CBZ, 4CC0, 4CC1

  • PubMed Abstract: 

    The Notch pathway is a core cell-cell signaling system in metazoan organisms with key roles in cell-fate determination, stem cell maintenance, immune system activation, and angiogenesis. Signals are initiated by extracellular interactions of the Notch receptor with Delta/Serrate/Lag-2 (DSL) ligands, whose structure is highly conserved throughout evolution. To date, no structure or activity has been associated with the extreme N termini of the ligands, even though numerous mutations in this region of Jagged-1 ligand lead to human disease. Here, we demonstrate that the N terminus of human Jagged-1 is a C2 phospholipid recognition domain that binds phospholipid bilayers in a calcium-dependent fashion. Furthermore, we show that this activity is shared by a member of the other class of Notch ligands, human Delta-like-1, and the evolutionary distant Drosophila Serrate. Targeted mutagenesis of Jagged-1 C2 domain residues implicated in calcium-dependent phospholipid binding leaves Notch interactions intact but can reduce Notch activation. These results reveal an important and previously unsuspected role for phospholipid recognition in control of this key signaling system.


  • Organizational Affiliation

    Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PROTEIN JAGGED-1
A, B
312Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P78504 (Homo sapiens)
Explore P78504 
Go to UniProtKB:  P78504
PHAROS:  P78504
GTEx:  ENSG00000101384 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP78504
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.206 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 56.93α = 95.04
b = 59.84β = 101.9
c = 62.94γ = 98.7
Software Package:
Software NamePurpose
BUSTERrefinement

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-11-27
    Type: Initial release
  • Version 1.1: 2013-12-11
    Changes: Database references
  • Version 1.2: 2013-12-18
    Changes: Database references
  • Version 1.3: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Other, Structure summary
  • Version 1.4: 2023-12-20
    Changes: Data collection, Database references, Refinement description, Structure summary