LIGAND & SUBUNIT INTERACTIONS OF TRANSMEMBRANE RECEPTORS

描述：(改编自申请人的摘要)跨膜信号转导是一种 所有活细胞共有的过程。工作计划描述了这一点 应用程序旨在发现受体之间的扩展交互作用 在化学感觉通路中，亚基对于跨膜信号传导很重要。 大肠埃希氏菌。由于这些相互作用似乎是 信号传递过程，对它们的深入了解可能会导致对 跨双层沟通机制的根本重要性 细胞。 现有证据表明，跨双层通信可以在 在某些情况下，相互稳定两者上的配体结合作用 在膜的侧面，并且在其他情况下预测通信 是相互破坏稳定的。这一概念将通过以下方式进行检验 分子间配基结合和蛋白质相互作用的测定 受体及其各种配体。这些实验旨在测试 一种配体对另一种配体结合的影响。 除了对系统的平衡研究外，系统的动力学 亚基的组装和拆卸将得到更深入的研究，因为最近 结果表明，组装/拆卸过程是一个配体催化的过程。 过程，并且可以在与信令相关的时间尺度上发生。这些数据将 用于区分两种跨膜信号模式，其中一种模式 化学感受器和相关的信号蛋白在一个稳定组装的 另一种是受体复合体动态地结合和 在信号时标上解离。

DESCRIPTION: (adapted from applicant's abstract) Transmembrane signaling is a process common to all living cells. The program of work described this application is designed to discover how extended interactions between receptor subunits are important for transmembrane signaling in the chemosensory pathway of Escherichia coli. Since these interactions appear to be an essential part of the signaling process, a deeper understanding of them may lead to insights of fundamental importance to the mechanism of trans-bilayer communication in all cells. The available evidence suggests that the trans-bilayer communication can, under some circumstances, mutually stabilize the ligand binding interaction on both sides of the membrane, and in other situations the communication is predicted to be mutually destabilizing. This concept will be put to the test with measurements of ligand binding and protein-protein interaction between the receptor, and its various ligands. The experiments are designed to test the influence of one ligand on the binding of others. In addition to an equilibrium investigation of the system, the dynamics of subunit assembly and disassembly will be more thoroughly studied, since recent results indicate that the assembly/disassembly process is a ligand-catalyzed process, and can occur on a time scale relevant for signaling. These data will be used to distinguish two models of transmembrane signaling, one in which the chemoreceptors and the associated signaling proteins are in a stably-assembled complex, and another in which the receptor complexes dynamically associate and dissociate on the signaling time scale.