Abstract:
:Endogenous lectins can control critical biological responses, including cell communication, signaling, angiogenesis and immunity by decoding glycan-containing information on a variety of cellular receptors and the extracellular matrix. Galectin-1 (Gal-1), a prototype member of the galectin family, displays only one carbohydrate recognition domain and occurs in a subtle homodimerization equilibrium at physiologic concentrations. Such equilibrium critically governs the function of this lectin signaling by allowing tunable interactions with a preferential set of glycosylated receptors. Here, we used a combination of experimental and computational approaches to analyze the kinetics and mechanisms connecting Gal-1 ligand unbinding and dimer dissociation processes. Kinetic constants of both processes were found to differ by an order of magnitude. By means of steered molecular dynamics simulations, the ligand unbinding process was followed monitoring water occupancy changes. By determining the water sites in a carbohydrate binding place during the unbinding process, we found that rupture of ligand-protein interactions induces an increase in energy barrier while ligand unbinding process takes place, whereas the entry of water molecules to the binding groove and further occupation of their corresponding water sites contributes to lowering of the energy barrier. Moreover, our findings suggested local asymmetries between the two subunits in the dimer structure detected at a nanosecond timescale. Thus, integration of experimental and computational data allowed a more complete understanding of lectin ligand binding and dimerization processes, suggesting new insights into the relationship between Gal-1 structure and function and renewing the discussion on the biophysics and biochemistry of lectin-ligand lattices.
journal_name
Glycobiologyjournal_title
Glycobiologyauthors
Romero JM,Trujillo M,Estrin DA,Rabinovich GA,Di Lella Sdoi
10.1093/glycob/cww052subject
Has Abstractpub_date
2016-12-01 00:00:00pages
1317-1327issue
12eissn
0959-6658issn
1460-2423pii
cww052journal_volume
26pub_type
杂志文章相关文献
GLYCOBIOLOGY文献大全abstract::In this paper, we present two complementary strategies for enrichment of glycoproteins on living cells that combine the desirable attributes of "robust enrichment" afforded by covalent-labeling techniques and "specificity for glycoproteins" typically provided by lectin or antibody affinity reagents. Our strategy invol...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/cws144
更新日期:2013-02-01 00:00:00
abstract::Viscumin of mistletoe (Viscum album L.) has a concentration-dependent activity profile unique to plant AB-toxins. It starts with lectin-dependent mitogenicity and then covers toxicity and cell agglutination, associated with shifts in the monomer/dimer equilibrium. Each lectin subunit harbors two sections for ligand co...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/cwl017
更新日期:2006-10-01 00:00:00
abstract::Rod and cone photoreceptors project from the outer retinal surface into a carbohydrate-rich interphotoreceptor matrix (IPM). Unique IPM glycoconjugates are distributed around rods and cones. Wheat germ agglutinin (WGA) strongly decorates the rod matrix domains and weakly decorates the cone matrix domains. This study c...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/8.10.997
更新日期:1998-10-01 00:00:00
abstract::The glycobiology of Schistosoma mansoni is dominated by developmentally regulated expression of various fucosylated structures, most notably the Lewis X epitope and a multifucosylated sequence, Fuc alpha1-->2Fuc alpha1-->, in its various forms. For the infective cercarial stage, Lewis X has been structurally identifie...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/11.5.395
更新日期:2001-05-01 00:00:00
abstract::Recent studies have shown that O-mannosyl glycans are present in several mammalian glycoproteins. Although knowledge on the functional roles of these glycans is accumulating, their biosynthetic pathways are poorly understood. Here we report the identification and initial characterization of a novel enzyme capable of f...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/11.1.37
更新日期:2001-01-01 00:00:00
abstract::Vesicular integral protein of 36 kDa (VIP36) is an intracellular lectin recognizing high-mannose type glycans and is highly expressed in salivary glands, especially the parotid gland, which secretes alpha-amylase in large quantities. Here immunoelectron microscopy demonstrated that VIP36 was primarily localized to sec...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/cwh082
更新日期:2004-08-01 00:00:00
abstract::To investigate the developmental role of complex N-linked oligosaccharides, we previously inactivated the mouse Mgat1 gene which encodes UDP-N-acetylglucosamine: alpha-3-D-mannoside beta-1,2-N-acetylglucosaminyltransferase I (GlcNAc-TI). Mgat1-null embryos developed morphogenic abnormalities by embryonic day (E) 9.5 a...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/5.5.535
更新日期:1995-07-01 00:00:00
abstract::Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy which can cause acute quadriplegia. Infection with micro-organisms, including Campylobacter jejuni (C. jejuni), Haemophilus influenzae, and Cytomegalovirus (CMV), is recognized as a main triggering event for the disease. Lipooligosacchari...
journal_title:Glycobiology
pub_type: 杂志文章,评审
doi:10.1093/glycob/cwp027
更新日期:2009-07-01 00:00:00
abstract::Artocarpus lakoocha agglutinin (ALA), isolated from the seeds of A. lakoocha fruit, is a galactose-binding lectin and a potent mitogen of T and B cells. Knowledge obtained from previous studies on the affinity of ALA was limited to molecular and submolecular levels of Galbeta1-->3GalNAc (T) and its derivatives. In the...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/cwh144
更新日期:2005-01-01 00:00:00
abstract::Lutrophin (LH) consists of an array of isoforms with different charges and bioactivities. This study was undertaken to clarify specifically how oligosaccharides of alpha and beta subunits contribute to LH isoform charges. Porcine LH (pLH) was separated into four isoforms by isoelectric focusing (IEF), followed by subu...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/2.3.225
更新日期:1992-06-01 00:00:00
abstract::Giardia lamblia, the protist that causes diarrhea, makes an Asn-linked-glycan (N-glycan) precursor that contains just two sugars (GlcNAc(2)) attached by a pyrophosphate linkage to a polyprenol lipid. Because the candidate cis-prenyltransferase of Giardia appears to be more similar to bacterial enzymes than to those of...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/cwq036
更新日期:2010-07-01 00:00:00
abstract::The endoplasmic reticulum malectin is a highly conserved protein in the animal kingdom that has no counterpart so far in lower organisms. We recently determined the structure of its conserved domain and found a highly selective binding to Glc(2)Man(9)GlcNAc(2), an intermediate of N-glycosylation. In our quest for puta...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/cwq059
更新日期:2010-08-01 00:00:00
abstract::Apiose is a unique branched-chain pentose found principally in plants. It is a key component of structurally complex cell wall polysaccharides, as well as being present in a large number of naturally occurring secondary metabolites. This review provides a comprehensive overview of the current state of knowledge on the...
journal_title:Glycobiology
pub_type: 杂志文章,评审
doi:10.1093/glycob/cww012
更新日期:2016-05-01 00:00:00
abstract::Neisseria meningitidis serogroups A, B, C, Y, W135 and X are responsible for most cases of meningococcal meningitis. Neisseria meningitidis serogroup X has recently emerged as a contributor to outbreaks of disease in Africa, but there is currently no vaccine against serogroup X. Understanding of the biosynthesis of th...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/cwt091
更新日期:2014-02-01 00:00:00
abstract::Lens culinaris lectin (LCA) is a useful probe for the detection in serum of a core-fucosylated alpha-fetoprotein, called AFP-L3 fraction, which is a well-known marker for the diagnosis and prognosis of hepatocellular carcinoma. Here we performed a systematic quantitative interaction analysis of LCA and its close homol...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/cwp016
更新日期:2009-05-01 00:00:00
abstract::Mouse gene knockout studies have provided unimpeachable evidence of immune-relevant functions for several sialyltransferase enzymes including ST6Gal I, ST3Gal I, and ST3Gal IV. Such studies cannot, however, identify cellular mechanisms for regulating such activities. In this article we provide evidence that murine B l...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/cwh133
更新日期:2004-12-01 00:00:00
abstract::Poly-N-acetyllactosamine extensions on N- and O-linked glycans are increasingly recognized as biologically important structural features, but access to these structures has not been widely available. Here, we report a detailed substrate specificity and catalytic efficiency of the bacterial β3-N-acetylglucosaminyltrans...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/cws101
更新日期:2012-11-01 00:00:00
abstract::The syp locus includes four genes encoding putative regulators, six genes encoding glycosyltransferases, two encoding export proteins, and six other genes encoding unidentified functional proteins associated with biofilm formation and symbiotic colonization. However, the individual functions of the respective genes re...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/cwu001
更新日期:2014-04-01 00:00:00
abstract::Xanthomonas translucens pv. translucens (Xtt) is a Gram-negative pathogen of crops from the plant family Poaceae. The lipopolysaccharide (LPS) of Xtt was isolated and chemically characterized. The analyses revealed the presence of rhamnose, xylose, mannose, glucose, galacturonic acid, phosphates, 3-deoxy-D-manno-oct-2...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/cww093
更新日期:2017-03-15 00:00:00
abstract::Multivalency in lectins is a phenomenon that has been discussed at considerable length. The structural basis for the role of multivalency in garlic lectin has been investigated here through computational studies. Biochemical studies have shown that the binding affinity of garlic lectin for high mannose oligosaccharide...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/cwg095
更新日期:2003-11-01 00:00:00
abstract::Schistosoma mansoni soluble egg antigens (SEAs) are crucially involved in modulating the host immune response to infection by S. mansoni. We report that human dendritic cells bind SEAs through the C-type lectin dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN). Monoclonal antibodies against the carbohydrat...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/cwg052
更新日期:2003-06-01 00:00:00
abstract::The presence of nonmammalian core alpha(1,3)-fucose and core xylose glyco-epitopes on glycans N-linked to therapeutic glycoproteins produced in plants has raised the question of their immunogenicity in human therapy. We address this question by studying the distribution of these N-glycans in pea, rice, and maize (whic...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/cwg024
更新日期:2003-06-01 00:00:00
abstract::Heparan sulfate/heparin N-deacetylase/N-sulfotransferase-1 (NDST-1) is a critical enzyme involved in heparan sulfate/heparin biosynthesis. This dual-function enzyme modifies the GlcNAc-GlcA disaccharide repeating sugar backbone to make N-sulfated heparosan. N-sulfation is an absolute requirement for the subsequent epi...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/cwh129
更新日期:2004-12-01 00:00:00
abstract::Cancer-associated glycan structures can be both tumor markers and engines of disease progression. The structure Siaα2,6Galβ1,4GlcNAc (Sia6LacNAc), synthesized by sialyltransferase ST6GAL1, is a cancer-associated glycan. Although ST6GAL1/Sia6LacNAc are often overexpressed in colorectal cancer (CRC), their biological an...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/cwz053
更新日期:2019-09-20 00:00:00
abstract::A rapid and reproducible method was developed to detect and quantify carbohydrate-mediated cell adhesion to glycans arrayed on glass slides. Monosaccharides and oligosaccharides were covalently attached to glass slides in 1.7-mm-diameter spots (200 spots/slide) separated by a Teflon gasket. Primary chicken hepatocytes...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/cwh022
更新日期:2004-02-01 00:00:00
abstract::Cell-surface glycans are functional docking sites for tissue lectins such as the members of the galectin family. This interaction triggers a wide variety of responses; hence, there is a keen interest in defining its structural features. Toward this aim, we have used enzyme-linked lectinosorbent (ELLSA) and inhibition ...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/cwj102
更新日期:2006-06-01 00:00:00
abstract::N-acetylglucosaminyltransferase V, encoded by the Mgat5 gene, plays an important regulatory role in the synthesis of complex N-glycans, including the Lewis antigens. The elevated expression of this enzyme is regulated during development and is highly associated with cellular transformation and malignancy. In addition,...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/cwf040
更新日期:2002-07-01 00:00:00
abstract::Diabetes mellitus was induced in one group of rats by a single injection of streptozotocin. The glycemia, the body weight, and the blood systolic pressure were measured every week, and the 24 h urine volume and urinary excretions of creatinine, albumin and glycosaminoglycans were measured every 2 weeks. At the end of ...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/10.2.185
更新日期:2000-02-01 00:00:00
abstract::Detailed structural and functional studies over the last decade have led to current recognition of the mycobacterial lipoarabinomannan (LAM) as a phosphatidylinositol anchored lipoglycan with diverse biological activities. Fatty acylation has been demonstrated to be essential for LAM to maintain its functional integri...
journal_title:Glycobiology
pub_type: 杂志文章,评审
doi:10.1093/glycob/8.2.113
更新日期:1998-02-01 00:00:00
abstract::Galectin-3 is a galactose-binding lectin that has been found in several mammalian tissues. Galectin-3 gene is expressed in a wide range of normal and tumoral cells. In the case of myeloid cells, its expression correlates with the differentiation of monocytes to macrophages. In the case of cancer cell lines, its expres...
journal_title:Glycobiology
pub_type: 杂志文章
doi:10.1093/glycob/7.8.1089
更新日期:1997-12-01 00:00:00