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PDBsum entry 4cc1
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Signaling protein
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PDB id
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4cc1
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PDB id:
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| Name: |
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Signaling protein
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Title:
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Notch ligand, jagged-1, contains an n-terminal c2 domain
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Structure:
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Protein jagged-1. Chain: a, b. Fragment: residues 32-335. Synonym: jagged1, hj1, cd339. Engineered: yes. Other_details: NAG linkage at n217 in both a, b chains, fuc linkage at t311 in a chain
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek 293s
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Resolution:
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2.84Å
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R-factor:
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0.199
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R-free:
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0.249
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Authors:
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C.R.Chilakuri,D.Sheppard,M.X.G.Ilagan,L.R.Holt,F.Abbott,S.Liang, R.Kopan,P.A.Handford,S.M.Lea
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Key ref:
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C.R.Chillakuri
et al.
(2013).
Structural analysis uncovers lipid-binding properties of Notch ligands.
Cell Rep,
5,
861-867.
PubMed id:
DOI:
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Date:
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17-Oct-13
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Release date:
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27-Nov-13
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PROCHECK
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Headers
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References
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P78504
(JAG1_HUMAN) -
Protein jagged-1 from Homo sapiens
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Seq:
Struc:
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1218 a.a.
306 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 2 residue positions (black
crosses)
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DOI no:
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Cell Rep
5:861-867
(2013)
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PubMed id:
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Structural analysis uncovers lipid-binding properties of Notch ligands.
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C.R.Chillakuri,
D.Sheppard,
M.X.Ilagan,
L.R.Holt,
F.Abbott,
S.Liang,
R.Kopan,
P.A.Handford,
S.M.Lea.
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ABSTRACT
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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.
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Links
