Liquid-liquid phase separation and extracellular multivalent interactions in the tale of galectin-3

Yi Ping Chiu, Yung Chen Sun, De Chen Qiu, Yu Hao Lin, Yin Quan Chen, Jean Cheng Kuo, Jie rong Huang*

*此作品的通信作者

研究成果: Article同行評審

56 引文 斯高帕斯(Scopus)

摘要

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.

原文English
文章編號1229
期刊Nature Communications
11
發行號1
DOIs
出版狀態Published - 1 12月 2020

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