Article ; Online: Liquid-liquid phase separation and extracellular multivalent interactions in the tale of galectin-3.
2020 Volume 11, Issue 1, Page(s) 1229
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 ... ...
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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MeSH term(s) | Agglutination ; Galectin 3/metabolism ; Glycosylation ; Intrinsically Disordered Proteins/metabolism ; Lipopolysaccharides/metabolism ; Micelles ; Protein Aggregates ; Protein Domains |
Chemical Substances | Galectin 3 ; Intrinsically Disordered Proteins ; LGALS3 protein, human ; Lipopolysaccharides ; Micelles ; Protein Aggregates |
Language | English |
Publishing date | 2020-03-06 |
Publishing country | England |
Document type | Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media |
ZDB-ID | 2553671-0 |
ISSN | 2041-1723 ; 2041-1723 |
ISSN (online) | 2041-1723 |
ISSN | 2041-1723 |
DOI | 10.1038/s41467-020-15007-3 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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