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

Author

Listed:
  • Yi-Ping Chiu

    (National Yang-Ming University)

  • Yung-Chen Sun

    (National Yang-Ming University)

  • De-Chen Qiu

    (National Yang-Ming University)

  • Yu-Hao Lin

    (National Yang-Ming University)

  • Yin-Quan Chen

    (National Yang-Ming University)

  • Jean-Cheng Kuo

    (National Yang-Ming University
    National Yang-Ming University)

  • Jie-rong Huang

    (National Yang-Ming University
    National Yang-Ming University)

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.

Suggested Citation

  • Yi-Ping Chiu & Yung-Chen Sun & De-Chen Qiu & Yu-Hao Lin & Yin-Quan Chen & Jean-Cheng Kuo & Jie-rong Huang, 2020. "Liquid-liquid phase separation and extracellular multivalent interactions in the tale of galectin-3," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15007-3
    DOI: 10.1038/s41467-020-15007-3
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    Cited by:

    1. Thapakorn Jaroentomeechai & Richard Karlsson & Felix Goerdeler & Fallen Kai Yik Teoh & Magnus Nørregaard Grønset & Dylan Wit & Yen-Hsi Chen & Sanae Furukawa & Venetia Psomiadou & Ramon Hurtado-Guerrer, 2024. "Mammalian cell-based production of glycans, glycopeptides and glycomodules," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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