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

Nature Communications
Yi-Ping ChiuJie-Rong Huang

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.

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Citations

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Methods Mentioned

BETA
glycosylation
fluorescence recovery after photobleaching
fluorescence microscopy
NMR
chemical shift

Software Mentioned

PScore Predictor
PONDR
NMRPipe
SPARKY
PLAAC
BLAST
Metamorph

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