LIGAND & SUBUNIT INTERACTIONS OF TRANSMEMBRANE RECEPTORS

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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.