KINETIC ANALYSIS OF TOXIN-RECEPTOR INTERACTIONS

Los Alamos Nat Secty-Los Alamos Nat Lab, Los Alamos NM

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Many critical biological reactions occur in or on bilayer membrane surfaces. An important class of such reactions is the interactions between soluble ligands and their cell-surface receptors. Ligand-receptor interactions may be monovalent, as is the case for small peptide ligands, bivalent, as for many large peptide hormones and antibodies, or of even higher valencies. In the latter class are the interactions between many bacterial toxins and their cell-surface receptors. Cholera toxin entry into mammalian cells, for example is mediated by binding of the pentameric B subunit to ganglioside Gm1 in the cell membrane. Notable features of this interaction include a low affinity monovalent interaction between individual B subunits and the carbohydrate moiety of Gm1, a high affinity multivalent interaction between pentameric B subunit with several membrane-bound Gm1 molecules, and the lateral mobility of the Gm1 molecule within the bilayer membrane. We have recently extended our studies on immobilized bialyers to the study of toxin processing in live cells. Using kinetic and temperature controlled flow cytometry, we are investigating the rates and capacities of various internalization pathways in live cells. These results are being used to build and test models of intracellular ligand processing.