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- Title
Liquid-liquid phase separation and extracellular multivalent interactions in the tale of galectin-3.
- Authors
Chiu, Yi-Ping; Sun, Yung-Chen; Qiu, De-Chen; Lin, Yu-Hao; Chen, Yin-Quan; Kuo, Jean-Cheng; Huang, Jie-rong
- Abstract
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. Galectin-3 consists of an unstructured N-terminal domain (NTD) and a structured carbohydrate-recognition domain and agglutinates neutrophils and glycosylated molecules in the extracellular milieu. Here the authors combine biophysical and biochemical experiments with NMR measurements and show that the galectin-3 NTD undergoes liquid-liquid phase separation (LLPS) and agglutinates other molecules through this process.
- Subjects
GALECTINS; PHASE separation; TYROSINE; DRUG design; TRYPTOPHAN; CARBOHYDRATES
- Publication
Nature Communications, 2020, Vol 11, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-020-15007-3