Thermodynamic binding studies of galectin-1, -3 and -7.
TL;DR: The results show important differences in the specificities of these three galectins toward poly-N-acetyllactosamine epitopes found on the surface of cells.
Abstract: The carbohydrate binding specificities of the galectin family of animal lectins has been the source of intense recent investigations. Isothermal titration microcalorimetry (ITC) provides direct determination of the thermodynamics of binding of carbohydrates to lectins, and has provided important insights into the fine carbohydrate binding specificities of a wide number of plant and animal lectins. Recent ITC studies have been performed with galectin-1, galectin-3 and galectin-7 and their interactions with sialylated and non-sialylated carbohydrates. The results show important differences in the specificities of these three galectins toward poly-N-acetyllactosamine epitopes found on the surface of cells. Published in 2004.
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TL;DR: A brief introduction to the galectins as a protein family with some comments on nomenclature is given.
Abstract: Good evidence suggest roles of galectins in cancer, immunity and inflammation, and development, but a unifying picture of their biological function is lacking. Instead galectins appear to have a particularly diverse, bewildering but intriguing array of activities both inside and outside cells—“clear truths and mysteries are inextricably twined”. Fortunately this has not discouraged but rather enthused a large number of good galectin researchers, some of which have contributed to this special issue of Glycoconjugate Journal to provide a personal, critical status of the field. Here we will give a brief introduction to the galectins as a protein family with some comments on nomenclature. Published in 2004.
653 citations
Cites background from "Thermodynamic binding studies of ga..."
...Polylactosamines with linearly repeated LacNAc residues have been suggested to be preferred high affinity ligands for galectin-1 [49], but at the same time other studies suggest that galectin-1 binds preferentially terminal LacNAc residues in sites C and D with A and B empty [ 46 ,50]....
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...In this volume papers by Ogawa et al. [41], and by Brewer [ 46 ] cover interesting cases of galectin structure and specificity....
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TL;DR: Based on the current knowledge of the composition of the glycome and the size of GBP binding sites, glycoproteins and glycolipids may contain approximately 3000 glycan determinants with an additional approximately 4000 theoretical pentasaccharide sequences in glycosaminoglycans, which provide an achievable target for new chemical and/or enzymatic syntheses.
Abstract: The number of glycan determinants that comprise the human glycome is not known. This uncertainty arises from limited knowledge of the total number of distinct glycans and glycan structures in the human glycome, as well as limited information about the glycan determinants recognized by glycan-binding proteins (GBPs), which include lectins, receptors, toxins, microbial adhesins, antibodies, and enzymes. Available evidence indicates that GBP binding sites may accommodate glycan determinants made up of 2 to 6 linear monosaccharides, together with their potential side chains containing other sugars and modifications, such as sulfation, phosphorylation, and acetylation. Glycosaminoglycans, including heparin and heparan sulfate, comprise repeating disaccharide motifs, where a linear sequence of 5 to 6 monosaccharides may be required for recognition. Based on our current knowledge of the composition of the glycome and the size of GBP binding sites, glycoproteins and glycolipids may contain ∼3000 glycan determinants with an additional ∼4000 theoretical pentasaccharide sequences in glycosaminoglycans. These numbers provide an achievable target for new chemical and/or enzymatic syntheses, and raise new challenges for defining the total glycome and the determinants recognized by GBPs.
442 citations
TL;DR: It is demonstrated that each of these galectins mechanistically differ in their binding to glycans on the microarrays and that these differences are reflected in the determinants required for cell binding and signaling.
377 citations
TL;DR: This review discusses systematically the general approaches that are available in developing carbohydrate sensors and “binders/receptors,” and their applications, with a focus on discoveries during the last 5 years.
Abstract: Carbohydrates are known to mediate a large number of biological and pathological events. Small and macromolecules capable of carbohydrate recognition have great potentials as research tools, diagnostics, vectors for targeted delivery of therapeutic and imaging agents, and therapeutic agents. However, this potential is far from being realized. One key issue is the difficulty in the development of "binders" capable of specific recognition of carbohydrates of biological relevance. This review discusses systematically the general approaches that are available in developing carbohydrate sensors and "binders/receptors," and their applications. The focus is on discoveries during the last 5 years.
257 citations
TL;DR: Data suggest that galectin-3 lattices are robust and could, thus, be involved, as previously proposed, in the restriction of receptor clustering, and lattice formation.
215 citations
References
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TL;DR: Examination of transcripts induced by p53 expression before the onset of apoptosis stimulated additional biochemical and pharmacological experiments suggesting that p53 results in apoptosis through a three-step process: the transcriptional induction of redox-related genes; the formation of reactive oxygen species; and the oxidative degradation of mitochondrial components, culminating in cell death.
Abstract: The inactivation of the p53 gene in a large proportion of human cancers has inspired an intense search for the encoded protein's physiological and biological properties. Expression of p53 induces either a stable growth arrest or programmed cell death (apoptosis). In human colorectal cancers, the growth arrest is dependent on the transcriptional induction of the protein p21WAF1/CIP1(ref. 1), but the mechanisms underlying the development of p53-dependent apoptosis are largely unknown2. As the most well documented biochemical property of p53 is its ability to activate transcription of genes, we examined in detail the transcripts induced by p53 expression before the onset of apoptosis. Of 7,202 transcripts identified, only 14 (0.19%) were found to be markedly increased in p53-expressing cells compared with control cells. Strikingly, many of these genes were predicted to encode proteins that could generate or respond to oxidative stress, including one that is implicated in apoptosis in plant meristems. These observations stimulated additional biochemical and pharmacological experiments suggesting that p53 results in apoptosis through a three-step process: (1) the transcriptional induction of redox-related genes; (2) the formation of reactive oxygen species; and (3) the oxidative degradation of mitochondrial components, culminating in cell death.
2,469 citations
1,480 citations
TL;DR: Crystallographic studies revealed that galectins and legume lectins such as concanavalin A have a common topology in spite of the absence of sequence homology, which suggests a possible relationship between animal and plant lectins, and the existence of a lectin super family.
Abstract: Galectins, animal lectins exhibiting specificity for galactosides, are now known to be widely distributed from lower invertebrates, such as sponges and nematodes, to higher vertebrates. The origin of the family can be traced back to the Precambrian era. They are classified into proto-, chimera-, and tandem-repeat types on the basis of protein architecture. The molecular functions of these types should be different because they can cross-link pairs of biomolecules of different combinations. Their biological significance, however, is not yet fully understood because they are involved in too many phenomena, such as differentiation, morphogenesis, metastasis, etc., and too many problems remain unsolved, such as those regarding their controversial cellular localization, mechanism of externalization, etc. Nevertheless, such difficulties seem to indicate their importance as household equipment and their common roles throughout the animal kingdom. They are likely to be responsible for recognizing the N-acetyllactosamine (LacNAc) structure, which is included in various glycoconjugates and considered to be an important glycocode, and then carry out appropriate tasks under given circumstances. Recently, crystallographic studies revealed that galectins and legume lectins such as concanavalin A have a common topology in spite of the absence of sequence homology. This suggests a possible relationship between animal and plant lectins, and the existence of a lectin super family. Studies on the galectin family are becoming increasingly important for glycobiology.
473 citations
TL;DR: The x-ray crystal structure of the human galectin-3 CRD, in complex with lactose and N-acetyllactosamine, at 2.1-A resolution was reported in this paper.
378 citations
Journal Article•
TL;DR: It is determined that galectin-1 binds to a restricted set of T cell surface glycoproteins, and that only CD45, CD43, and CD7 appear to directly participate in galectIn-1-induced apoptosis.
Abstract: Galectin-1 induces apoptosis of human thymocytes and activated T cells by an unknown mechanism. Apoptosis is a novel function for a mammalian lectin; moreover, given the ubiquitous distribution of the oligosaccharide ligand recognized by galectin-1, it is not clear how susceptibility to and signaling by galectin-1 is regulated. We have determined that galectin-1 binds to a restricted set of T cell surface glycoproteins, and that only CD45, CD43, and CD7 appear to directly participate in galectin-1-induced apoptosis. To determine whether these specific glycoproteins interact cooperatively or independently to deliver the galectin-1 death signal, we examined the cell surface localization of CD45, CD43, CD7, and CD3 after galectin-1 binding to human T cell lines and human thymocytes. We found that galectin-1 binding resulted in a dramatic redistribution of these glycoproteins into segregated membrane microdomains on the cell surface. CD45 and CD3 colocalized on large islands on apoptotic blebs protruding from the cell surface. These islands also included externalized phosphatidylserine. In addition, the exposure of phosphatidylserine on the surface of galectin-1-treated cells occurred very rapidly. CD7 and CD43 colocalized in small patches away from the membrane blebs, which excluded externalized phosphatidylserine. Receptor segregation was not seen on cells that did not die in response to galectin-1, including mature thymocytes, suggesting that spatial redistribution of receptors into specific microdomains is required for triggering apoptosis.
346 citations