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Updated: Oct 21, 2026

Complementation of Splicing Activity by a Galectin-3 - U1 snRNP Complex on Beads
Published on: December 9, 2020
Gal-3 N-terminal prolines within residues 69 to 117 regulate CRD glycan binding, phase separation and Gal-3-mediated
Zhen He1, Xiaomeng Wang1, Dongmei Wang1
1Engineering Research Center of Glycoconjugates Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun, 130024, China.
Abstract:
Galectin-3 (Gal-3), the only chimeric galectin, is a central driver and potential biomarker for cancer progression, fibrotic disorders, and heart failure. As a key proinflammatory factor, Gal-3 aggravates various disease states by promoting immune cell activation, cytokine storm amplification, and cell migration. Previously, we reported on the structural and functional role of prolines within Gal-3 NT residues 1-68. Here, we report on how the 14 NT prolines within the 69-117 segment affect Gal-3 structure and function. Circular dichroism (CD) and fluorescence spectroscopies showed that none of these proline-to-alanine substitutions altered overall Gal-3 conformation, whereas some of them did modulate glycoprotein-induced phase separation and ligand binding (lactose (Lac), LacNAc, (LacNAc)3), as well as Gal-3-mediated cell function, i.e., cell activation, hemagglutination, and endocytosis. Three of these prolines were found to be the most crucial to Gal-3-mediated activities, with P86A and P113A attenuating glycan-binding, glycoprotein-induced phase separation, and cellular function and P117A enhancing these processes. Correlation analysis of all prolines within the Gal-3 NT revealed that prolines within the 1-68 segment primarily modulate cellular function via glycan binding, whereas prolines within the 69-117 segment modulate glycan-induced phase separation and cellular function. Overall, our findings reveal distinct functional roles for specific Gal-3 NT prolines, provide mechanistic insight into Gal-3 structure-function relationships, and identify potential NT prolines as targets for ameliorating various Gal-3-related pathological disorders.
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