Binding of a Soluble meso-Tetraarylporphyrin to Human Galectin-7 Induces Oligomerization and Modulates Its Pro-Apoptotic Activity,Biochemistry

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Binding of a Soluble meso-Tetraarylporphyrin to Human Galectin-7 Induces Oligomerization and Modulates Its Pro-Apoptotic Activity
Biochemistry ( IF 2.9 ) Pub Date : 2020-11-24 , DOI: 10.1021/acs.biochem.0c00736
Yossef López de Los Santos ₁ , David N Bernard ₁ , Philippe Egesborg ₁ , Myriam Létourneau ₁ , Clara Lafortune ₁ , Matthew J Cuneo ₂ , Agathe Urvoas ₃ , David Chatenet ₁ , Jean-Pierre Mahy ₄ , Yves St-Pierre ₁ , Rémy Ricoux ₄ , Nicolas Doucet _{1,

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Affiliation

The selective targeting of protein–protein interactions remains a significant determinant for the proper modulation and regulation of cell apoptosis. Prototypic galectins such as human galectin-7 (GAL-7) are characterized by their ability to form homodimers that control the molecular fate of a cell by mediating subtle yet critical glycan-dependent interactions between pro- and anti-apoptotic molecular partners. Altering the structural architecture of GAL-7 can therefore result in resistance to apoptosis in various human cancer cells, further illustrating its importance in cell survival. In this study, we used a combination of biophysical and cellular assays to illustrate that binding of a water-soluble meso-tetraarylporphyrin molecule to GAL-7 induces protein oligomerization and modulation of GAL-7-induced apoptosis in human Jurkat T cells. Our results suggest that the integrity of the GAL-7 homodimer architecture is essential for its molecular function, in addition to providing an interesting porphyrin binding modulator for controlling apoptosis in mammalian cells.

中文翻译：

可溶性内消旋四芳基卟啉与人半乳糖凝集素 7 的结合诱导寡聚化并调节其促凋亡活性

蛋白质-蛋白质相互作用的选择性靶向仍然是适当调节和调节细胞凋亡的重要决定因素。原型半乳糖凝集素如人半乳糖凝集素-7 (GAL-7) 的特征在于它们能够形成同源二聚体，通过介导促凋亡和抗凋亡分子伙伴之间微妙但关键的聚糖依赖性相互作用来控制细胞的分子命运。因此，改变 GAL-7 的结构可以导致各种人类癌细胞对细胞凋亡的抵抗，进一步说明其在细胞存活中的重要性。在这项研究中，我们结合使用了生物物理和细胞分析来说明水溶性中间体的结合-四芳基卟啉分子对 GAL-7 诱导蛋白质寡聚化和 GAL-7 诱导的人类 Jurkat T 细胞凋亡的调节。我们的结果表明，GAL-7 同源二聚体结构的完整性对其分子功能至关重要，此外还提供有趣的卟啉结合调节剂以控制哺乳动物细胞的凋亡。

更新日期：2020-12-08

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