Institute of Biochemistry and Molecular Biology, National Yang-Ming University, No. 155 Section 2 Li-nong Street, Taipei, 11221, Taiwan.
Cancer Progression Research Center, National Yang-Ming University, No. 155 Section 2 Li-nong Street, Taipei, 11221, Taiwan.
Nat Commun. 2020 Mar 6;11(1):1229. doi: 10.1038/s41467-020-15007-3.
Liquid-liquid phase separation (LLPS) explains many intracellular activities, but its role in extracellular functions has not been studied to the same extent. Here we report how LLPS mediates the extracellular function of galectin-3, the only monomeric member of the galectin family. The mechanism through which galectin-3 agglutinates (acting as a "bridge" to aggregate glycosylated molecules) is largely unknown. Our data show that its N-terminal domain (NTD) undergoes LLPS driven by interactions between its aromatic residues (two tryptophans and 10 tyrosines). Our lipopolysaccharide (LPS) micelle model shows that the NTDs form multiple weak interactions to other galectin-3 and then aggregate LPS micelles. Aggregation is reversed when interactions between the LPS and the carbohydrate recognition domains are blocked by lactose. The proposed mechanism explains many of galectin-3's functions and suggests that the aromatic residues in the NTD are interesting drug design targets.
液-液相分离（LLPS）解释了许多细胞内活动，但它在细胞外功能中的作用尚未得到同等程度的研究。在这里，我们报告了 LLPS 如何介导半乳糖凝集素-3 的细胞外功能，半乳糖凝集素-3 是半乳糖凝集素家族中唯一的单体成员。半乳糖凝集素-3 凝集（充当聚集糖基化分子的“桥梁”）的机制在很大程度上是未知的。我们的数据表明，其 N 端结构域（NTD）通过其芳香族残基（两个色氨酸和 10 个酪氨酸）之间的相互作用发生 LLPS。我们的脂多糖（LPS）胶束模型表明，NTD 与其他半乳糖凝集素-3 形成多个弱相互作用，然后聚集 LPS 胶束。当乳糖阻断 LPS 与碳水化合物识别结构域之间的相互作用时，聚集被逆转。所提出的机制解释了半乳糖凝集素-3 的许多功能，并表明 NTD 中的芳香族残基是有趣的药物设计靶点。
