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Query: UNIPROT:P17931 (galectin-3)
 2,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Embryos of the frog Xenopus laevis at cleavage, blastula, gastrula and neurula stages contain a galactose-specific lectin. Extracts of gastrula embryos show the highest specific activity for this lectin compared to the other stages. Haemagglutinating activity of crude extracts is inhibited by lactose, alpha-galactose, beta-galactose, alpha Gal(1----4) beta Gal, beta Gal(1----3) alpha GalNAc, beta Gal(1----3) beta GlcNAc, beta Gal (1----4) beta GlcNAc, and most effectively by the disaccharide alpha Gal(1----3) beta Gal. Lectin from all stages was purified by absorption to galactose-linked immunoadsorbent or by affinity chromatography on a column of p-aminophenyl-beta-D-lactoside coupled to Sepharose 4B. In order to identify a single lectin band under reducing conditions in sodium dodecyl sulphate/polyacrylamide electrophoresis SDS/PAGE, it was necessary to treat aqueous suspensions of the purified lectin with chloroform/methanol (2:1, v/v). The lectin remained in the aqueous layer and gave rise on SDS/PAGE to a distinct band of 65 500 +/- 2780 molecular weight. Aqueous suspensions of the purified lectin that were not subjected to extraction with chloroform/methanol gave rise to several bands. Isoelectric focussing of the purified lectin resulted in two bands that separated at pI 4.3 and 4.5. In aqueous solution in the presence of lactose the chloroform/methanol-treated lectin appears to be an aggregate of apparent molecular weight of 375 000; the non-treated lectin under the same conditions has an apparent molecular weight of 490 000.
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PMID:Studies on the endogenous galactose-binding lectin during early development of the embryo of Xenopus laevis. 383 62

Some natural (Gal-Cer, Lac-Cer, desyalylated gangliosides) and synthetic (HMGal) glycolipids differing in the length of the bridge linking the terminal galactose with the hydrophobic moiety were incorporated into the liposome membranes. The precipitation of the thus obtained vesicles induced by galactose-specific lectin RCA was studied. It was shown that when the amount of the glycolipids used for the incorporation into the liposomes (1 mol. %) was the same, the vesicles with HMGal or Gal-Cer incorporated into them did not precipitate in the presence of lectin, whereas the liposomes with incorporated Lac-Cer or desyalylated gangliosides did precipitate. It was thus concluded that in order for galactose-containing liposomes precipitation by lectin RCA1 to be induced, galactose should be separated from the liposome membrane with a distance not less than 7 A. The nature of lectin-induced nonspecific precipitation of ganglioside-containing liposomes, ganglioside mycelles and cardiolipin-lecithine liposomes containing lactosylceramide was investigated. Some nonspecific ionic interactions of negatively charged liposomes and ganglioside mycelles with lectin were observed, which disappeared with a rise in the NaCl concentration up to 150-200 mM.
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PMID:[Separate factors influencing the interaction of carbohydrate- containing liposomes with galactose-specific lectins]. 652 64

Galectin-3 (Gal-3) is a beta-galactoside-binding protein with M(r) approximately 30,000. Cell surface Gal-3 is postulated to be involved in homotypic aggregation of tumor cells in the circulation during metastasis through attachment to a complementary serum glycoprotein(s), which serves as a cross-linking bridge between adjacent cells. To test this hypothesis a recombinant strain of baculovirus encoding Gal-3 was used to infect Sf9 insect cells, which lack endogenous Gal-3. Immunoblotting and indirect immunofluorescence studies revealed that the infection with recombinant virus conferred Gal-3 expression on Sf9 cells, and the Gal-3 was localized on the cell surface as well as in the cytoplasm. Sf9 cells infected with recombinant virus underwent homotypic aggregation in the presence of exogenous glycoprotein (i.e., asialofetuin), whereas control cells uninfected or infected with wild-type virus did not. Lactose and Fab' fragments of anti-Gal-3 antibodies markedly inhibited the cell-cell aggregation. Moreover, cosuspension of Sf9 cells infected with the recombinant virus with uninfected cells in the presence of asialofetuin resulted in a preferential cell-cell adhesion of the Gal-3-expressing cells. These results directly demonstrate the ability of cell surface Gal-3 molecules to mediate homotypic cell adhesion by bridging through branched, soluble complementary glycoconjugates.
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PMID:Functional evidence that cell surface galectin-3 mediates homotypic cell adhesion. 754 67

The Mac-2 protein is a lectin specific for galactose-containing glycoconjugates. Present in some normal cells, it was also associated with the metastatic potential of some carcinoma cells. We studied Mac-2 expression in three human melanoma cell lines and in five variants and clones from one of them. By using the M3/38 rat monoclonal antibody, Mac-2 was demonstrated on cell surface by flow cytometry as well as in the cytoplasm and in the nucleus by confocal microscopy. The expression of Mac-2 was not correlated with that of terminal unsialylated Gal beta 1-3 GalNac structures on metastatic melanoma cell lines. However, the presence of extracellular Mac-2 containing vesicles was observed in cell lines with metastatic potency. Western blot analysis of cell lysates, in reducing or non-reducing conditions, revealed two bands of 34-36 and 93-98 kDa apparent M(r), also found in HL60 and P388.D1 cell lines used as positive controls.
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PMID:Expression of the galactose binding protein Mac-2 by human melanoma cell-lines. 801 32

The carbohydrate binding specificity of recombinant carbohydrate-binding protein 35 (rCBP35) has been investigated by quantitative precipitation using a series of glycoproteins and carbohydrate-protein conjugates and by inhibition of precipitation using well defined carbohydrate haptens. Synthetic glycoconjugates and glycoproteins containing terminal nonreducing galactosyl units in beta-linkage were capable of forming a precipitate with rCBP35. If the glycoprotein or glycoconjugate contained terminal Neu5Ac, or galactose in alpha-linkage, precipitate formation was not observed. We also found that murine laminin, which contains polylactosamine structures, reacted more strongly than did bovine fetuin. Using carbohydrate-bovine serum albumin (BSA) glycoconjugates, we found that the tetrasaccharide Gal beta 1, 4GlcNAc beta 1, 3Gal beta 1,4-GlcNAc-BSA reacted more strongly than the disaccharide Gal beta 1, 4GlcNAc-BSA conjugate, suggesting that the binding site accommodates carbohydrate ligands greater in size than a disaccharide. Equilibrium dialysis experiments using [3H]lactose showed that rCBP35 binds 1 mol (n = 0.84) of lactose/30,000 g atoms of protein, with an affinity constant of 2.07 x 10(4) M-1. The binding site on the polypeptide appears to contain four subsites that recognize the sequence Gal beta 1,4GlcNAc beta 1, Gal beta 1,X-. All disaccharides tested that contain a nonreducing beta-galactosyl unit behaved as inhibitors of precipitation at approximately the same concentration, suggesting that the reducing position of the tetrasaccharide does not play an important role in the specific binding to the fourth subsite. The reducing sugar may serve to hold the saccharide in a tunnel like binding pocket since methyl-beta-D-galactoside itself is an extremely poor inhibitor.
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PMID:Carbohydrate-binding protein 35. II. Analysis of the interaction of the recombinant polypeptide with saccharides. 832 71

Bark lectins from the elderberry species belonging to the genus Sambucus have a unique carbohydrate binding specificity for sialylated glycoconjugates containing NeuAc(alpha 2-6)Gal/GalNAc sequence. To elucidate the structure of the elderberry lectin, a cDNA library was constructed from the mRNA isolated from the bark tissue of Japanese elderberry (Sambucus sieboldiana) with lambda gt11 phage and screened with anti-S. sieboldiana agglutinin (SSA) antibody. The nucleotide sequence of a cDNA clone encoding full-length SSA (LecSSA1) showed the presence of an open reading frame with 1902 base pairs, which corresponded to 570 amino acid residues. This open reading frame encoded a signal peptide and a linker region (19 amino acid residues) between the two subunits of SSA, the hydrophobic (A-chain) and hydrophilic (B-chain) subunits. This indicates that SSA is synthesized as a preproprotein and post-translationally cleaved into two mature subunits. Homology searching as well as molecular modeling studies unexpectedly revealed that each subunit of SSA has a highly homologous structure to the galactose-specific lectin subunit and ribosome-inactivating subunit of plant toxic proteins such as ricin and abrin, indicating a close evolutionary relationship between these carbohydrate-binding proteins.
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PMID:Sialylated oligosaccharide-specific plant lectin from Japanese elderberry (Sambucus sieboldiana) bark tissue has a homologous structure to type II ribosome-inactivating proteins, ricin and abrin. cDNA cloning and molecular modeling study. 857 42

The galactose-specific lectin present in the seeds of snake gourd (Trichosanthes anguina) was purified in high yield by affinity chromatography on cross-linked guar gum. The purified snake gourd seed lectin (SGSL) yielded a single symmetrical peak on gel filtration with an M(r) of 62 kDa and gave a single band in PAGE under non-denaturing conditions. In SDS-PAGE, SGSL gave a single band of M(r) 53 kDa in the absence of beta-mercaptoethanol, and two bands of M(r) 32 and 23 kDa in its presence, indicating that the lectin is a heterodimer in which the subunits are linked by a disulphide bridge. The lectin gave a single precipitin line in immunodiffusion experiments with antiserum raised against the purified SGSL. No cross-reactivity was found between SGSL and antiserum raised against the Momordica charantia lectin and vice versa, suggesting that the two lectins are antigenically dissimilar. Haemagglutination-inhibition data show that Me beta D-Gal is the best monosaccharide inhibitor of SGSL and indicate that an equatorial hydroxyl at C-2 and axial hydroxyl at C-4 in the pyranose form are important binding loci for the lectin.
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PMID:Purification in high yield and characterisation of the galactose-specific lectin from the seeds of snake gourd (Trichosanthes anguina). 879 50

A model of the carbohydrate recognition domain CRD, residues 111-245, of hamster galectin-3 has been made using homology modeling and dynamics minimization methods. The model is based on the known x-ray structures of bovine galectin-1 and human galectin-2. The oligosaccharides NeuNAc-alpha2,3-Gal-beta1,4-Glc and GalNAc-alpha1, 3-[Fuc-alpha1,2]-Gal-beta1,4-Glc, known to be specific high-affinity ligands for galectin-3, as well as lactose recognized by all galectins were docked in the galectin-3 CRD model structure and a minimized binding conformation found in each case. These studies indicate a putative extended carbohydrate-binding subsite in the hamster galectin-3 involving Arg139, Glu230, and Ser232 for NeuNAc-alpha2,3-; Arg139 and Glu160 for fucose-alpha1,2-; and Arg139 and Ile141 for GalNAc-alpha1,3- substituents on the primary galactose. Each of these positions is variable within the whole galectin family. Two of these residues, Arg139 and Ser232, were selected for mutagenesis to probe their importance in this newly identified putative subsite. Residue 139 adopts main-chain dihedral angles characteristic of an isolated bridge structural feature, while residue 232 is the C-terminal residue of beta-strand-11, and is followed immediately by an inverse gamma-turn. A systematic series of mutant proteins have been prepared to represent the residue variation present in the aligned sequences of galectins-1, -2, and -3. Minimized docked models were generated for each mutant in complex with NeuNAc-alpha2,3-Gal-beta1,4-Glc, GalNAc-alpha1, 3-[Fuc-alpha1,2]-Gal-beta1,4- Glc, and Gal-beta1,4-Glc. Correlation of the computed protein-carbohydrate interaction energies for each lectin-oligosaccharide pair with the experimentally determined binding affinities for fetuin and asialofetuin or the relative potencies of lactose and sialyllactose in inhibiting binding to asiolofetuin is consistent with the postulated key importance of Arg139 in recognition of the extended sialylated ligand.
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PMID:Evidence for subsites in the galectins involved in sugar binding at the nonreducing end of the central galactose of oligosaccharide ligands: sequence analysis, homology modeling and mutagenesis studies of hamster galectin-3. 945 Oct 13

Mapping of protein domains having a distinct function is essential to understanding the protein's structure-function relationship. We used a bacteriophage lambda surface expression vector, lambdafoo, in order to determine the minimal carbohydrate-binding domain of human galectin-3 (Gal-3). Gal-3 cDNA was randomly digested by DNase I and cloned into the phage vector. The library generated was screened by affinity selection using lactose immobilized on agarose beads. DNA sequence analysis of a set of isolated clones defined the minimal folding domain of Gal-3 required for lactose binding, which consisted of 136 amino-acid residues. Using the phage clones isolated, we also determined relative dissociation constants in solution between lactose and the minimal domain expressed on the phage surface. This technique does not require either purified or labeled proteins, and bacteriophage lambda surface display may, therefore, be useful for protein domain mapping and in vitro studies of various macromolecular interactions.
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PMID:Protein domain mapping by lambda phage display: the minimal lactose-binding domain of galectin-3. 1055 59

Nonenzymatic glycation has been implicated in the pathogenesis of the dysregulated tissue remodeling that characterizes diabetic glomerulopathy, via the formation of advanced glycation end products (AGEs) and their binding to cell surface receptors. Several AGE-binding proteins have been identified so far, including p60, p90, and the adhesive and growth-regulating lectin galectin-3 (Gal-3), the components of the so-called AGE-receptor complex. This study aimed to evaluate the mesangial expression of the AGE-receptor complex and its modulation by the diabetic milieu, both in vivo, in non-diabetic versus streptozotocin-induced diabetic rats, and in vitro, in mesangial cells exposed to either normal glucose (NG) levels (5.5 mmol/l), as compared with high glucose (HG) levels (30 mmol/l) and iso-osmolar mannitol (M), or to native bovine serum albumin (BSA), as compared with glycated BSA with AGE formation (BSA-AGE) and glycated BSA in which AGE formation was prevented by aminoguanidine (BSA-AM). In vivo, Gal-3 protein and mRNA were not detectable in glomeruli from nondiabetic rats until 12 months after initiating the study. On the contrary, in diabetic rats, Gal-3 expression was observed at 2 months of disease duration, and it increased thereafter. Both p60 and p90 immunoreactivities were observed at the glomerular level with slightly increased expression of p90, but not p60, in diabetic versus nondiabetic animals. In vitro, Gal-3 was not detectable in mesangial cells cultured in NG (although it became evident after a certain number of passages in culture), whereas Gal-3 was detectable in cells grown on BSA. Prolonged exposure (2-4 weeks) of mesangial cells to HG but not to M, as well as growing cells on BSA-AGE and, to a lesser extent, BSA-AM, induced or significantly increased the expression of Gal-3, both protein (up to 2.65-fold) and mRNA (up to 3.10-fold) and its secretion in the medium (by approximately 50%). Both p60 and p90 were demonstrated in mesangial cells under NG conditions, and the expression of p90, but not p60, was upregulated by approximately 20% by HG or BSA-AGE. These results indicate that 1) under basal conditions, Gal-3, unlike p90 and p60, is not detectable in the mesangium but becomes expressed with aging and 2) the diabetic milieu induces or upregulates Gal-3 production, whereas it increases only slightly the expression of p90, but not p60. Gal-3 expression or overexpression may modulate the AGE-receptor-mediated events by modifying the function of the AGE-receptor complex. Additionally, it may exert direct effects on tissue remodeling by virtue of its adhesive and growth-regulating properties.
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PMID:The diabetic milieu modulates the advanced glycation end product-receptor complex in the mesangium by inducing or upregulating galectin-3 expression. 1090 85


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