Comparison of the Interaction of Mono- and Oligovalent Ligands with Cholera Toxin. Demonstration of Aggregate Formation at Low Ligand Concentrations

Schwarzmann, Günter; Mraz, W.; Sattler, Jörg; Schindler, R. N.; Wiegandt, Herbert

doi:10.1515/bchm2.1978.359.2.1277

Cited by 28 publications

(6 citation statements)

References 16 publications

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“…The value of CMC for GMl is still at great variance, since recent reports give values as disparate as lo-' M (Formisano et al, 1979) and M (Rauvala, 1979). Moreover, as for other amphiphiles (Menger, 1979), it has been suggested that, besides the monomeric and the micellar form, gangliosides may also occur as aggregates smaller than micelles (oligomers) (Schwarzmann et al, 1978;Formisano et al, 1979).…”

Section: Discussionmentioning

confidence: 99%

Interactions of G_M1 Ganglioside with Crude Rat Brain Neuronal Membranes

Toffano

Benvegnù

Bonetti

et al. 1980

Journal of Neurochemistry

142

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The binding of GM1 ganglioside to crude preparations of rat brain neuronal membranes was studied, the following results being obtained: (a) the binding process followed a biphasic kinetics, which displayed a break at 0.07-0.08 x 10(-6) M GM1 concentration; (b) the features of the binding process at GM1 concentrations below the break and, over the break, above 10(-6) M appeared to be different. Below the break the process proceeded slowly and brought a stable and irreversible association of GM1 molecules to the membranes. Over 10(-6) M the process was much more rapid and caused GM1 molecules to interact in such a way that they were releasable by washing and could exchange with newly added free ganglioside; (c) the two binding processes displayed the characteristics of a saturation phenomenon; (d) in both cases, GM1 taken up was freely available to galactose oxidase, indicating that the oligosaccharide chains protrude from the membrane surface. We postulate that GM1 occurs, below and above the break, in different physical forms, each of them having a different mechanism of interaction with the membrane. Above 10(-6) M GM1 interacts as micelles, and the basis of the micelle-membrane interaction is a fusion process. Below the break, in the 10(-8)--10(-7) M range, the binding is the result of hydrophobic interactions between sites on the membrane and the hydrophobic portion of individual ganglioside molecules, most likely in the monomeric form.

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Section: Discussionmentioning

confidence: 99%

Interactions of G_M1 Ganglioside with Crude Rat Brain Neuronal Membranes

Toffano

Benvegnù

Bonetti

et al. 1980

Journal of Neurochemistry

142

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“…Due to its high five-fold symmetry and the fact that it has five identical binding sites for GM1. A first attempt to improve oGM1 affinity using multivalency was reported by Schwarzmann et al (1978), who designed and synthesized divalent oGM1 that has better affinity to CTB than oGM1 by itself. More recently, Schengrund et al (1989) prepared highly active multivalent o-GM1 ligands by linking them to a polymer (poly-L-lisine) or to a dendrimer (octapropyleneimine) that serves as a core.…”

Section: Design Of Multivalent Inhibitorsmentioning

confidence: 99%

Structure Based Design of Cholera Toxin Antagonists

Podlipnik¹,

Reina²

2012

Cholera

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“…Choleragen is precipitated from solution by GM1 , forms a precipitation band with the ganglioside in agar diffusion gels, cosediments with it in the ultracentrifuge, and binds to GM1 that has been absorbed to plastic tubes [56,61,63,66,117,122].…”

Section: Cholera Toxin Binds To Gm1 In Model Systemsmentioning

confidence: 99%

“…Binding is multivalent with each toxin molecule binding to four to six oligosaccharide chains [34,117]; presumably, there is one binding site on each of the five polypeptides of the B component. In the presence of GMl-oligosaccharide, choleragen and its B component exhibited shifts in their fluorescence and circular dichroic spectra [34].…”

Section: Cholera Toxin Binds To Gm1 In Model Systemsmentioning

confidence: 99%

Role of membrane gangliosides in the binding and action of bacterial toxins

1982

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Gangliosides are complex glycosphingolipids that contain from one to several residues of sialic acid. They are present in the plasma membrane of vertebrate cells with their oligosaccharide chains exposed to the external environment. They have been implicated as cell surface receptors and several bacterial toxins have been shown to interact with them. Cholera toxin, which mediates its effects on cells by activating adenylate cyclase, bind with high affinity and specificity to ganglioside GM1. Toxin-resistant cells which lack GM1 can be sensitized to cholera toxin by treating them with GM1. Cholera toxin specifically protects GM1 from cell surface labeling procedures and only GM1 is recovered when toxin-receptor complexes are isolated by immunoadsorption. These results clearly demonstrate that GM1 is the specific and only receptor for cholera toxin. Although cholera toxin binds to GM1 on the external side of the plasma membrane, it activates adenylate cyclase on the cytoplasmic side of the membrane by ADP-ribosylation of the regulatory component of the cyclase. GM1 in addition to functioning as a binding site for the toxin appears to facilitate its transmembrane movement. The heat-labile enterotoxin of E. coli is very similar to cholera toxin in both form and function and can also use GM1 as a cell surface receptor. The potent neurotoxin, tetanus toxin, has a high affinity for gangliosides GD1b and GT1b and binds to neurons which contain these gangliosides. It is not yet clear whether these gangliosides are the physiological receptors for tetanus toxin. By applying the techniques that established GM1 as the receptor for cholera toxin, the role of gangliosides as receptors for tetanus toxin as well as physiological effectors may be elucidated.

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Comparison of the Interaction of Mono- and Oligovalent Ligands with Cholera Toxin. Demonstration of Aggregate Formation at Low Ligand Concentrations

Cited by 28 publications

References 16 publications

Interactions of G_M1 Ganglioside with Crude Rat Brain Neuronal Membranes

Interactions of G_M1 Ganglioside with Crude Rat Brain Neuronal Membranes

Structure Based Design of Cholera Toxin Antagonists

Role of membrane gangliosides in the binding and action of bacterial toxins

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Comparison of the Interaction of Mono- and Oligovalent Ligands with Cholera Toxin. Demonstration of Aggregate Formation at Low Ligand Concentrations

Cited by 28 publications

References 16 publications

Interactions of GM1 Ganglioside with Crude Rat Brain Neuronal Membranes

Interactions of GM1 Ganglioside with Crude Rat Brain Neuronal Membranes

Structure Based Design of Cholera Toxin Antagonists

Role of membrane gangliosides in the binding and action of bacterial toxins

Contact Info

Product

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Interactions of G_M1 Ganglioside with Crude Rat Brain Neuronal Membranes

Interactions of G_M1 Ganglioside with Crude Rat Brain Neuronal Membranes