Liquid-liquid phase separation and extracellular multivalent interactions in the tale of galectin-3
Liquid-liquid phase separation and extracellular multivalent interactions in the tale of galectin-3
复制标题
DOI：
10.1038/s41467-020-15007-3
复制
发表时间：
2020-03-06
影响因子：
16.6
通讯作者：
Huang, Jie-rong
中科院分区：
文献类型：
--
作者：
Chiu, Yi-Ping;Sun, Yung-Chen;Huang, Jie-rong
液-液相分离（LLPS）解释了许多细胞内活动，但其在细胞外功能中的作用尚未得到相同程度的研究。在这里，我们报告了LLPS如何介导半乳凝素-3（半乳凝素家族中唯一的单体成员）的细胞外功能。半乳糖凝集素-3凝集（作为聚集糖基化分子的“桥梁”）的机制在很大程度上是未知的。我们的数据表明，它的N-末端结构域（NTD）经历LLPS驱动的芳香族残基（两个Dahans和10个酪氨酸）之间的相互作用。我们的脂多糖（LPS）胶束模型表明，NTDs形成多个弱相互作用的其他半乳糖凝集素3，然后聚集LPS胶束。当LPS和碳水化合物识别结构域之间的相互作用被乳糖阻断时，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目标。
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.