Liquid-liquid phase separation and extracellular multivalent interactions in the tale of galectin-3
Open Access
- 6 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 11 (1), 1-12
- https://doi.org/10.1038/s41467-020-15007-3
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.Funding Information
- Ministry of Science and Technology, Taiwan (108-2113-M-010-005)
This publication has 84 references indexed in Scilit:
- Ligand Induced Galectin-3 Protein Self-associationOnline Journal of Public Health Informatics, 2012
- Cell-free Formation of RNA Granules: Low Complexity Sequence Domains Form Dynamic Fibers within HydrogelsCell, 2012
- Phase transitions in the assembly of multivalent signalling proteinsNature, 2012
- LPS-Induced Galectin-3 Oligomerization Results in Enhancement of Neutrophil ActivationPLOS ONE, 2011
- Concerted regulation of focal adhesion dynamics by galectin-3 and tyrosine-phosphorylated caveolin-1The Journal of cell biology, 2008
- Galectin Binding to Mgat5-Modified N-Glycans Regulates Fibronectin Matrix Remodeling in Tumor CellsMolecular and Cellular Biology, 2006
- Determination of critical micelle concentrations and aggregation numbers by fluorescence correlation spectroscopy: Aggregation of a lipopolysaccharideAnalytica Chimica Acta, 2006
- Interfaces and the driving force of hydrophobic assemblyNature, 2005
- The origin and evolution of model organismsNature Reviews Genetics, 2002
- NMRPipe: A multidimensional spectral processing system based on UNIX pipesJournal of Biomolecular NMR, 1995