6RLC

Crystal structure of the PDZ tandem of syntenin in complex with fragment F13

Summary for 6RLC

• Entry DOI: 10.2210/pdb6rlc/pdb
• Descriptor: Syntenin-1, (2~{S})-2-[3-(4-chlorophenyl)sulfanylpropanoylamino]-3-methyl-butanoic acid, ACETATE ION, ... (4 entities in total)
• Functional Keywords: signaling protein cell adhesion pdz domain syntenin syndecan drug design, signaling protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 73515.15

Authors

Feracci, M.,Barral, K. (deposition date: 2019-05-02, release date: 2021-02-03, Last modification date: 2024-05-15)

Primary citation

Leblanc, R.,Kashyap, R.,Barral, K.,Egea-Jimenez, A.L.,Kovalskyy, D.,Feracci, M.,Garcia, M.,Derviaux, C.,Betzi, S.,Ghossoub, R.,Platonov, M.,Roche, P.,Morelli, X.,Hoffer, L.,Zimmermann, P.
Pharmacological inhibition of syntenin PDZ2 domain impairs breast cancer cell activities and exosome loadifing with syndecan and EpCAM cargo.
J Extracell Vesicles, 10:e12039-e12039, 2020

PubMed Abstract: 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 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.

PubMed: 33343836
DOI: 10.1002/jev2.12039

Experimental method

X-RAY DIFFRACTION (2.2 Å)