6R9H

Crystal structure of the PDZ tandem of syntenin in complex with fragment C58

6R9H の概要

• エントリーDOI: 10.2210/pdb6r9h/pdb
• 分子名称: Syntenin-1, PHOSPHATE ION, (2~{S})-2-[2-(4-chlorophenyl)sulfanylethanoylamino]-3-methyl-butanoic acid, ... (5 entities in total)
• 機能のキーワード: signaling protein cell adhesion pdz domain syntenin syndecan drug design, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 73235.35

構造登録者

Feracci, M.,Barral, K. (登録日: 2019-04-03, 公開日: 2021-02-03, 最終更新日: 2024-01-24)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2 Å)