KINETIC ANALYSIS OF TOXIN-RECEPTOR INTERACTIONS

毒素-受体相互作用的动力学分析

• 批准号: 8361745
• 负责人: STEVEN W GRAVES
• 金额: $ 1.12万
• 依托单位: LOS ALAMOS NAT SECTY-LOS ALAMOS NAT LAB
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361745
• 关键词: Affinity; Bacterial Toxins; Binding; Biological; Carbohydrates; Cell Surface Receptors; Cell membrane; Cells; Cholera Toxin; Flow Cytometry; Funding; Gangliosides; Grant; Individual; Kinetics; Lateral; Life; Ligands; Mammalian Cell; Mediating; Membrane; Modeling; National Center for Research Resources; Pathway interactions; Peptide antibodies; Peptides; Principal Investigator; Process; Reaction; Research; Research Infrastructure; Resources; Sorting - Cell Movement; Source; Surface; Temperature; Testing; Toxin; United States National Institutes of Health; cost; peptide hormone; receptor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 许多关键的生物反应发生在双层膜表面上。 一类重要的反应是可溶性配体及其细胞表面受体之间的相互作用。 配体 - 受体相互作用可能是单价的，与许多大型肽激素和抗体，甚至更高的价值一样，小肽配体的情况也是如此。 在后一类中是许多细菌毒素及其细胞表面受体之间的相互作用。 例如，霍乱毒素进入哺乳动物细胞，例如，五聚体B亚基与细胞膜中的神经节GM1结合而介导。 这种相互作用的显着特征包括单个B亚基与GM1的碳水化合物部分之间的亲和力一价相互作用，GM1的碳水化合物部分是五聚体B亚基与几个膜结合的GM1分子之间的高亲和力多价相互作用，以及BiLayerermbrane内部GM1分子的几个膜结合的GM1分子。 我们最近将有关固定双赖酯的研究扩展到了活细胞中毒素加工的研究。 使用动力学和温度控制的流式细胞仪，我们正在研究活细胞中各种内部化途径的速率和能力。 这些结果用于构建和测试细胞内配体处理的模型。