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PDBsum entry 6r9h
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Signaling protein
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PDB id
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6r9h
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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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Crystal structure of the pdz tandem of syntenin in complex with fragment c58
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Structure:
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Syntenin-1. Chain: a, b, c, d. Synonym: melanoma differentiation-associated protein 9,mda-9,pro-tgf- alpha cytoplasmic domain-interacting protein 18,tacip18,scaffold protein pbp1,syndecan-binding protein 1. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: sdcbp, mda9, sycl. Expressed in: escherichia coli k-12. Expression_system_taxid: 83333
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Resolution:
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2.00Å
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R-factor:
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0.212
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R-free:
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0.246
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Authors:
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M.Feracci,K.Barral
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Key ref:
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R.Leblanc
et al.
(2020).
Pharmacological inhibition of syntenin PDZ2 domain impairs breast cancer cell activities and exosome loading with syndecan and EpCAM cargo.
J Extracell Vesicles,
10,
e12039.
PubMed id:
DOI:
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Date:
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03-Apr-19
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Release date:
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03-Feb-21
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PROCHECK
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Headers
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References
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O00560
(SDCB1_HUMAN) -
Syntenin-1 from Homo sapiens
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Seq:
Struc:
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298 a.a.
162 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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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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J Extracell Vesicles
10:e12039
(2020)
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PubMed id:
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Pharmacological inhibition of syntenin PDZ2 domain impairs breast cancer cell activities and exosome loading with syndecan and EpCAM cargo.
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R.Leblanc,
R.Kashyap,
K.Barral,
A.L.Egea-Jimenez,
D.Kovalskyy,
M.Feracci,
M.Garcia,
C.Derviaux,
S.Betzi,
R.Ghossoub,
M.Platonov,
P.Roche,
X.Morelli,
L.Hoffer,
P.Zimmermann.
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ABSTRACT
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Exosomes support cell-to-cell communication in physiology and disease, including
cancer. We currently lack tools, such as small chemicals, capable of modifying
exosome composition and activity in a specific manner. Building on our previous
understanding of how syntenin, and its PDZ partner syndecan (SDC), impact on
exosome composition we optimized a small chemical compound targeting the PDZ2
domain of syntenin. In vitro , in tests on MCF-7 breast carcinoma cells, this
compound is non-toxic and impairs cell proliferation, migration and primary
sphere formation. It does not affect the size or the number of secreted
particles, yet it decreases the amounts of exosomal syntenin, ALIX and SDC4
while leaving other exosomal markers unaffected. Interestingly, it also blocks
the sorting of EpCAM, a bona fide target used for carcinoma exosome
immunocapture. Our study highlights the first characterization of a small
pharmacological inhibitor of the syntenin-exosomal pathway, of potential
interest for exosome research and oncology.
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Links
