Structure of Galectin-3 bound to a model membrane containing ganglioside GM1.
Structure of Galectin-3 bound to a model membrane containing ganglioside GM1.
复制标题
Galectin-3 的结构与含有神经节苷脂 GM1 的模型膜结合。
DOI：
10.1016/j.bpj.2022.08.018
复制
发表时间：
2023
影响因子：
3.4
通讯作者：
Gabius,Hans-Joachim
中科院分区：
文献类型：
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作者：
VanderZanden,CrystalM;Majewski,Jaroslaw;Weissbarth,Yvonne;Browne,DanielleF;Watkins,ErikB;Gabius,Hans-Joachim
半乳糖凝集素-3（Galectin-3，Gal-3）是一种β-半乳糖苷酶结合蛋白，参与多种生物学过程，包括神经元的生长和粘附。Gal-3与神经节苷脂GM 1的五糖链在质膜外叶的配对，触发下游细胞信号级联反应，似乎参与了这些过程。Gal-3的一个重要特征是它能够形成连接各种碳水化合物修饰分子的低聚物和超分子组装体。虽然我们知道Gal-3与小的碳水化合物配体结合的原子结构，但仍不清楚Gal-3如何在膜中结合GM 1。此外，这种相互作用对Gal-3的结构和寡聚体组装的影响还有待阐明。在这项研究中，我们使用的X射线反射率（XR）从模型膜，以确定的结构和表面覆盖的Gal-3绑定到含有GM 1的膜。我们观察到糖识别结构域与GM 1的五糖相互作用，而N-末端结构域指向远离膜，可能有助于蛋白质-蛋白质相互作用。在含有20mol%GM 1的膜中，Gal-3覆盖膜表面的约50%，每2130 μ m2结合一个Gal-3分子。我们使用分子动力学模拟和Voronoi镶嵌算法来建立膜结合Gal-3的原子模型，这是由XR结果支持的。总的来说，这项工作提供了结构信息，描述了Gal-3如何结合GM 1的五糖链，这是触发神经元生长和粘附调节过程的先决条件。
Galectin-3 (Gal-3) is a β-galactosidase-binding protein involved in various biological processes, including neuronal growth and adhesion. The pairing of Gal-3 with ganglioside GM1's pentasaccharide chain at the outer leaflet of the plasma membrane, which triggers downstream cell-signaling cascades, seems to be involved in these processes. A crucial feature of Gal-3 is its ability to form oligomers and supramolecular assemblies that connect various carbohydrate-decorated molecules. Although we know the atomistic structure of Gal-3 bound to small carbohydrate ligands, it remains unclear how Gal-3 binds GM1 in a membrane. Furthermore, the influence of this interaction on Gal-3's structure and oligomeric assembly has to be elucidated. In this study, we used X-ray reflectivity (XR) from a model membrane to determine the structure and surface coverage of Gal-3 bound to a membrane containing GM1. We observed that the carbohydrate recognition domain interacts with GM1's pentasaccharide, while the N-terminal domain is pointed away from the membrane, likely to facilitate protein-protein interactions. In a membrane containing 20 mol % GM1, Gal-3 covered ∼50% of the membrane surface with one Gal-3 molecule bound per 2130 Å2. We used molecular dynamics simulations and Voronoi tessellation algorithms to build an atomistic model of membrane-bound Gal-3, which is supported by the XR results. Overall, this work provides structural information describing how Gal-3 can bind GM1's pentasaccharide chain, a prerequisite for triggering regulatory processes in neuronal growth and adhesion.