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Lee, Reiko T.; Lee, Yuan C.

doi:10.1023/a:1011070425430

Cited by 420 publications

(219 citation statements)

References 37 publications

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“…They found that the residual inhibition by the R118 mutant was also sialic acid-dependent. These data indicate that the R118-mutant MAG retains sufficient sialic acid binding to inhibit neurite outgrowth when the protein is expressed in a highly multivalent form on the surface of CHO cells (36).…”

Section: Discussionmentioning

confidence: 73%

Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein (MAG), an inhibitor of nerve regeneration

Vyas

Patel

Fromholt

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

253

199

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Myelin-associated glycoprotein (MAG) binds to the nerve cell surface and inhibits nerve regeneration. The nerve cell surface ligand(s) for MAG are not established, although sialic acid-bearing glycans have been implicated. We identify the nerve cell surface gangliosides GD1a and GT1b as specific functional ligands for MAG-mediated inhibition of neurite outgrowth from primary rat cerebellar granule neurons. MAG-mediated neurite outgrowth inhibition is attenuated by (i) neuraminidase treatment of the neurons; (ii) blocking neuronal ganglioside biosynthesis; (iii) genetically modifying the terminal structures of nerve cell surface gangliosides; and (iv) adding highly specific IgG-class antiganglioside mAbs. Furthermore, neurite outgrowth inhibition is mimicked by highly multivalent clustering of GD1a or GT1b by using precomplexed antiganglioside Abs. These data implicate the nerve cell surface gangliosides GD1a and GT1b as functional MAG ligands and suggest that the first step in MAG inhibition is multivalent ganglioside clustering.

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Section: Discussionmentioning

confidence: 73%

Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein (MAG), an inhibitor of nerve regeneration

Vyas

Patel

Fromholt

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

253

199

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“…The multiple subunits may endow multivalent binding properties to the MBP. This is of significant interest because it is well established that high affinity multivalent binding capable of clustering the receptors is often required for the biological function of most lectins (35,36).…”

Section: Discussionmentioning

confidence: 99%

Cloning and Characterization of a Novel Mannose-binding Protein of Acanthamoeba

Gárate

Cao

Bateman

et al. 2004

Journal of Biological Chemistry

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Acanthamoebae produce a painful, blinding infection of the cornea. The mannose-binding protein (MBP) of Acanthamoeba is thought to play a key role in the pathogenesis of the infection by mediating the adhesion of parasites to the host cells. We describe here the isolation and molecular cloning of Acanthamoeba MBP. The MBP was isolated by chromatography on the mannose affinity gel. Gel filtration experiments revealed that the Acanthamoeba lectin is a ϳ400-kDa protein that is constituted of multiple 130-kDa subunits. Cloning and sequencing experiments indicated that the Acanthamoeba MBP gene is composed of 6 exons and 5 introns that span 3.6 kb of the amoeba genome and that MBP cDNA codes for a precursor protein of 833 amino acids. That the cloned cDNA encodes authentic MBP was demonstrated by showing that: (i) recombinant MBP possesses mannose binding activity, and (ii) polyclonal antibodies prepared against Acanthamoeba MBP bound to the recombinant protein. Sequence analysis revealed that the MBP contains a large N-terminal extracellular domain, a transmembrane domain, and a short C-terminal cytoplasmic domain. Despite extensive BLAST searches using the MBP sequence, no significant matches were retrieved. The most striking feature of the Acanthamoeba MBP sequence is the presence of a cysteine-rich region containing 14 CXCXC motifs within the extracellular domain. In summary, we have isolated, cloned, and characterized a novel MBP from Acanthamoeba. Because the presence of antibodies to MBP in tears provides protection against infection, the availability of the MBP cDNA sequence and rMBP should help develop: (i) a tear-based test to identify individuals who are at risk of developing the keratitis and (ii) strategies to immunize high-risk individuals.Acanthamoebae are causative agents of two distinct disease entities. In immunocompromised individuals, this protozoan parasite produces chronic granulomatous amoebic encephalitis and disseminating infections including dermatitis and pneumonitis (1, 2). Granulomatous amoebic encephalitis is nearly always fatal because of the lack of an effective treatment. In immunocompetent individuals, Acanthamoebae provoke a debilitating vision-threatening corneal infection known as Acanthamoeba keratitis (AK) 1 (3-5). AK is characterized by intense pain and a slowly worsening clinical course. Contact lens wear is a major risk factor (3, 6, 7). In the developed world, ϳ85% of the cases are diagnosed in contact lens wearers (7). However, in the developing countries, where contact lens use is infrequent, the disease is more commonly found in non-contact lens wearers (8). The mechanism by which Acanthamoebae produce granulomatous amoebic encephalitis and AK has not been fully elucidated. It is generally accepted that the two major predisposing factors in the pathogenesis of AK are minor corneal trauma caused by contact lens wear or other noxious agents and exposure to contaminated solutions including lens care products and tap water (9, 10). The adhesion of parasites to the host cells ...

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“…In most cases, sialic acid binding lectins, which also include several viral glycoproteins and bacterial toxins (2,4), as well as the mammalian lectin superfamilies such as the siglecs (5) and selectins (6), bind to their receptor with relatively high affinity due to the multivalent nature of these molecules, thus alleviating the low intrinsic affinity that most protein-carbohydrate interactions are associated with (7,8). Generally, association constants (K a ) for the binding of monovalent and divalent sialosides by such lectins can reach 10 4 …”

mentioning

confidence: 99%

Enhancing the Receptor Affinity of the Sialic Acid-binding Domain of Vibrio cholerae Sialidase through Multivalency

Connaris

Crocker

Taylor

2009

Journal of Biological Chemistry

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Many glycoside hydrolases possess carbohydrate-binding modules (CBMs) that help target these enzymes to appropriate substrates and increase their catalytic efficiency. The Vibrio cholerae sialidase contains two CBMs, one of which is designated as a family CBM40 module and has been shown through structural and calorimetry studies to recognize the ␣-anomer of sialic acid with a K D of ϳ30 M at 37°C. The affinity of this V. cholerae CBM40 module for sialic acid is one of the highest reported for recognition of a monosaccharide by a CBM. As Nature often increases a weak substrate affinity through multivalency, we have explored the potential of developing reagents with an increased affinity for sialic acid receptors through linking CBM40 modules together. The V. cholerae CBM40 was subcloned and crystallized in the presence of sialyllactose confirming its ability to recognize sialic acid. Calorimetry revealed that this CBM40 demonstrated specificity to ␣(2,3)-, ␣(2,6)-, and ␣(2,8)-linked sialosides. Polypeptides containing up to four CBM40 modules in tandem were created to determine if an increase in affinity to sialic acid could be achieved through an avidity effect. Using SPR and a multivalent ␣(2,3)-sialyllactose ligand, we show that increasing the number of linked modules does increase the affinity for sialic acid. The four-CBM40 module protein has a 700-to 1500-fold increase in affinity compared with the single-CBM40 module. Varying the linker length of amino acids between each CBM40 module had little effect on the binding of these polypeptides. Finally, fluorescence-activated cell sorting analysis demonstrated that a green fluorescent protein fused to three CBM40 modules bound to subpopulations of human leukocytes. These studies lay the foundation for creating high affinity, multivalent CBMs that could have broad application in glycobiology.

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Cited by 420 publications

References 37 publications

Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein (MAG), an inhibitor of nerve regeneration

Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein (MAG), an inhibitor of nerve regeneration

Cloning and Characterization of a Novel Mannose-binding Protein of Acanthamoeba

Enhancing the Receptor Affinity of the Sialic Acid-binding Domain of Vibrio cholerae Sialidase through Multivalency

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