Glycan Dependence of Galectin-3 Self-Association Properties

Halimi, Hubert; Rigato, Annafrancesca; Byrne, Deborah; Ferracci, Géraldine; Sebban‐Kreuzer, Corinne; Elantak, Latifa; Guerlesquin, Françoise

doi:10.1371/journal.pone.0111836

Cited by 45 publications

(43 citation statements)

References 18 publications

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“…35,36 In addition, the glycodendrimers evaluated by Gabius and Roy presenting 90 lactose residues showed IC 50 values of 0.16 mM compared to 164 mM for the monovalent ligand, resulting in an inhibitory potency of 1025 and 11 per carbohydrate. 31 Several studies suggest that Gal-3 oligomerizes upon glycan binding through its N-terminal domain, 29,32,87 however, CRD mediated multimerization has also been described. [88][89][90] With multivalent glycans on cell surfaces, Gal-3 can induce cell-cell interactions, crosslink receptors and even form lattice on cell surfaces.…”

Section: Galectin-3 Binding Studiesmentioning

confidence: 99%

Effects of linker and liposome anchoring on lactose-functionalized glycomacromolecules as multivalent ligands for binding galectin-3

et al. 2019

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In this work, we present a bottom-up approach for the synthesis of lactose-functionalized glycomacromolecules and glycofunctionalized liposomes and apply these compounds to investigate their effects of multivalent presentation on binding to galectin-3.Step-wise assembly of tailor-made building blocks on solid supports was used to synthesize a series of oligo(amidoamine) scaffolds that were further conjugated to lactose via copper catalyzed 1,3-dipolar cycloaddition. Binding studies with galectin-3 revealed affinities in the micromolar range that increased with increasing carbohydrate valency, and decreased with increasing size and linker flexibility. To further explore their multivalency, selected glycomacromolecules were conjugated to lipids and used in liposomal formulations. Binding studies show a further increase in binding in nanomolar ranges in dependence of both ligand structure and liposomal presentation, demonstrating the power of combining the two approaches.

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Section: Galectin-3 Binding Studiesmentioning

confidence: 99%

Effects of linker and liposome anchoring on lactose-functionalized glycomacromolecules as multivalent ligands for binding galectin-3

et al. 2019

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“…Subsequently, galectin-3 molecules oligomerize through self-assembly of the non-CRD domains and become multivalent in glycan binding (Fig. 1B) (6)(7)(8)(9)(10)(11)(12). In addition to N-terminal-mediated oligomerization, CRD of galectin-3 selfassociates upon binding to its ligands, thereby contributing to positive cooperativity in the formation of multivalency (8,11,(13)(14)(15).…”

Section: A Galectins Accumulate In the Cytosol: Distinct Segregationmentioning

confidence: 99%

Cytosolic Galectins and Their Release and Roles as Carbohydrate-Binding Proteins in Host–Pathogen Interaction

Sato

2018

TIGG

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The glycocalyx is a layer of glycoconjugates found on the surface of both host cells and microorganisms. Information presented on some of the glycans on glycoconjugates is recognized by mammalian glycan-binding proteins, lectins, and these interactions modulate various physiological processes, including host innate immune responses. Lectins and host glycoconjugates are synthesized in the same secretory pathway. One notable exception is a family of soluble β-galactoside-binding lectins, galectins, which are synthesized and accumulated in the cytosol and thereby segregated from their glycan ligands. In cases where pathogenic infection persists and tissue injury occurs, galectins are passively released from injured cells. In addition, galectins are actively secreted through unconventional secretory pathways by inflammation-activated or differentiating cells. Thus, extracellular emergence of galectins is associated with the presence of pathogenic hazards. Evidence from a series of studies suggests that galectins exert multiple immunological effects. Extracellular galectin-3 acts as a damage-associated molecular pattern (DAMP) and adhesion molecule for neutrophils in lungs to initiate a proinflammatory response and to mediate rapid neutrophil migration in lungs infected with pathogenic microorganisms. In this review, the roles of galectin-3 in initial innate immune responses and resolution are discussed together with a historical overview of research on galectins in the secretory pathway and innate immunology. A. Galectins Accumulate in the Cytosol: Distinct Segregation from Glycan LigandsIn mammalian cells, the majority of glycans, i.e., oligosaccharides and polysaccharides, are covalently linked to either proteins Galectins are soluble, non-glycosylated lectins defined by a conserved carbohydrate recognition domain (CRD) that shows affinity for β-galactoside, especially glycans containing a number of lactosamine residues (Galβ1-4GlcNAc) (2-4). Detailed information on the carbohydrate binding specificity of galectins has been provided in the review by the group of Hirabayashi in the TIGG special issue 'Galectins updated' (5). In humans, 11 galectins have been identified to date (2). These proteins exhibit structural differences in the presentation of CRD (Fig. 1A). Some contain one CRD (prototype) and exist as either monomers or dimers while others (tandem repeats) contain two CRDs connected by a short linker region. Galectin-3 uniquely occurs as a chimeric protein with one CRD at the C-terminus and an additional non-CRD domain at the N-terminus, which is involved in its oligomerization.Upon binding to its glycan ligands, the conformation of galectin-3 appears altered. Subsequently, galectin-3 molecules oligomerize through self-assembly of the non-CRD domains and become multivalent in glycan binding (Fig. 1B) (6-12). In addition to N-terminal-mediated oligomerization, CRD of galectin-3 selfassociates upon binding to its ligands, thereby contributing to positive cooperativity in the formation of multivalency ...

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“…Galectin-3 is a chimeric, soluble β-galactoside binding lectin from the galectin family, with three distinct domains: a NH2-terminal domain, a proline-rich collagen-alpha-like domain, and a COOH-terminal domain containing the CRD [16,17,18,19]. The C-terminal domain allows binding to carbohydrate ligands, such as N-acetyllactosamine, while the N-terminal domain allows the formation of oligomers and interaction with cell mebranes or extracellular receptors, such as those found on macrophages or collagen IV, respectively [20,21].…”

Section: Galectin-3: Biological Background and Functionmentioning

confidence: 99%

“…These biomarkers are mostly found in the cytoplasm [27], but may also cross cellular and intracellular membranes, thus being able to enter the nucleus or mitochondria, to be expressed on the cell membrane or to pass into the extracellular space, and, subsequently, in the systemic circulation [27,28]. Cytosol galec-tin-3 inhibits apoptosis, and can be expelled from the cell by exocytosis, circumventing the Golgi apparatus and the endoplasmic reticulum, further having a tendency to bind to several extracellular matrix proteins, such as fibronectin, tenascin and laminin [21]. In the nucleus, galectin-3 is involved in splicing and cell proliferation, while when expressed on the surface of the cells, it has the ability to modulate cell survival and mRNA splicing [29].…”

Section: Galectin-3: Biological Background and Functionmentioning

confidence: 99%