Animal Lectins: Form, Functions and Clinical Applications (original) (raw)
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The involvement of galectins as pleiotropic regulators of cell adhesion and growth in disease progression explains the interest to define their ligand-binding properties. Toward this end, it is desirable to approach in vivo conditions to attain medical relevance. In order to simulate physiological conditions with cell surface glycans as recognition sites and galectins as mediators of intercellular contacts we developed an assay using galectin-loaded Raji cells. The extent of surface binding of fluorescent neoglycoconjugates depended on the lectin presence and the type of lectin, the nature of the probes' carbohydrate headgroup and the density of unsubstituted β-galactosides on the cell surface. Using the most frequently studied galectins-1 and -3, application of this assay led to rather equal binding levels for linear and branched oligomers of N-acetyllactosamine. A clear preference of galectin-3 for α1-3-linked galactosylated lactosamine was noted. In parallel, a panel of 24 neoglycoconjugates was tested as inhibitors of galectin binding from solution to N-glycans of surface-immobilized asialofetuin. These two assays differ in presentation of the galectin and ligand, facilitating identification of assay-dependent properties. Under the condition of the cell assay, selectivity among oligosaccharides for the lectins was higher, and extraordinary affinity of galectin-1 to 3 -O-sulfated probes in a solid-phase assay was lost in the cell assay. Having introduced and validated a cell assay, the comprehensive profiling of ligand binding to cell-surface-presented galectins is made possible.
Galectins: structure, function and therapeutic potential
Expert Reviews in Molecular Medicine, 2008
Galectins are a family of animal lectins that bind β-galactosides. Outside the cell, galectins bind to cell-surface and extracellular matrix glycans and thereby affect a variety of cellular processes. However, galectins are also detectable in the cytosol and nucleus, and may influence cellular functions such as intracellular signalling pathways through protein–protein interactions with other cytoplasmic and nuclear proteins. Current research indicates that galectins play important roles in diverse physiological and pathological processes, including immune and inflammatory responses, tumour development and progression, neural degeneration, atherosclerosis, diabetes, and wound repair. Some of these have been discovered or confirmed by using genetically engineered mice deficient in a particular galectin. Thus, galectins may be a therapeutic target or employed as therapeutic agents for inflammatory diseases, cancers and several other diseases.
Galectins. Structure and function of a large family of animal lectins
Journal of Biological Chemistry, 1994
Lectins are proteins that bind to specific carbohydrate structures and can thus recognize particular glycoconjugates among the vast array expressed in animal'tissues. Most animal lectins can be classified into four distinct families (1): C-type lectins (including the selectins); P-type lectins; pentraxins; and galectins (2), formerly known as S-type or S-Lac lectins (1). The purpose of this short review is to provide a framework for integrating the rapid increase in knowledge of the diversity, structure, and function of the galectins. While the emphasis here is on mammalian galectins, important advances are also being made in studies of galectins in other species, including nematode (3) and sponge (4). * This minireview will be reprinted in the Minireview Compendium, which will be available in December, 1994. The molecular gra hics images were produced using the Midasplus, FtibbonJr, Neon, and Ilagel programs from the Computer Gra
Evolving Mechanistic Insights into Galectin Functions
Methods in Molecular Biology, 2014
Galectins are an evolutionarily ancient family of glycan-binding proteins (GBPs) and are found in all animals. Although they were discovered over 30 years ago, ideas about their biological functions continue to evolve. Current evidence indicates that galectins, which are the only known GBPs that occur free in the cytoplasm and extracellularly, are involved in a variety of intracellular and extracellular pathways contributing to homeostasis, cellular turnover, cell adhesion, and immunity. Here we review evolving insights into galectin biology from a historical perspective and explore current evidence regarding biological roles of galectins.
Galectin-3: An open-ended story
Galectins, an ancient lectin family, are characterized by specific binding of β-galactosides through evolutionary conserved sequence elements of carbohydrate-recognition domain (CRD). A structurally unique member of the family is galectin-3; in addition to the CRD it contains a prolineand glycine-rich N-terminal domain (ND) through which is able to form oligomers. Galectin-3 is widely spread among different types of cells and tissues, found intracellularly in nucleus and cytoplasm or secreted via non-classical pathway outside of cell, thus being found on the cell surface or in the extracellular space. Through specific interactions with a variety of intra-and extracellular proteins galectin-3 affects numerous biological processes and seems to be involved in different physiological and pathophysiological conditions, such as development, immune reactions, and neoplastic transformation and metastasis. The review attempts to summarize the existing information on structural, biochemical and intriguing functional properties of galectin-3.
Generation and Use of Recombinant Galectins
Current Protocols, 2021
Galectins are soluble carbohydrate binding proteins that can bind β-galactosecontaining glycoconjugates by means of a conserved carbohydrate recognition domain (CRD). In mammalian systems, galectins have been shown to mediate very important roles in innate and adaptive immunity as well as facilitating host-pathogen relationships. Many of these studies have relied on purified recombinant galectins to uncover key features of galectin biology. A major limitation to this approach is that certain recombinant galectins purified using standard protocols are easily susceptible to loss of glycan-binding activity. As a result, biochemical studies that employ recombinant galectins can be misleading if the overall activity of a galectin remains unknown in a given assay condition. This article examines fundamental considerations when purifying galectins by lactosyl-sepharose and nickel-NTA affinity chromatography using human galectin-4N and-7 as examples, respectively. As other approaches are also commonly applied to galectin purification, we also discuss alternative strategies to galectin purification, using human galectin-1 and-9 as examples.
Glycobiology, 2018
Galectin-10 (Gal-10) which forms Charcot-Leyden crystals in vivo, is crucial to regulating lymph cell function. Here, we solved the crystal structures of Gal-10 and eight variants at resolutions of 1.55-2.00 Å. Structural analysis and size exclusion chromatography demonstrated that Gal-10 dimerizes with a novel global shape that is different from that of other prototype galectins (e.g., Gal-1, -2 and -7). In the Gal-10 dimer, Glu33 from one subunit modifies the carbohydrate-binding site of another, essentially inhibiting disaccharide binding. Nevertheless, glycerol (and possibly other small hydroxylated molecules) can interact with residues at the ligand binding site, with His53 being the most crucial for binding. Alanine substitution of the conserved Trp residue (Trp72) that is crucial to saccharide binding in other galectins, actually leads to enhanced erythrocyte agglutination, suggesting that Trp72 negatively regulates Gal-10 ligand binding. Overall, our crystallographic and bio...