MECHANISM OF ION TRANSPORT THROUGH MEMBRANE CHANNELS

这项拟议研究的目的是了解钠的化学基础

The goal of the proposed research is to understand the chemical basis for sodium and potassium fluxes across biological membranes. The questions will be approached using three types of channel-forming molecules of bacterial origin: cidins A, B, and C which associate as dimers to form transmembrane channels; (2) various chemically modified analogues includng covalently coupled homo-and heterodimers, of these same gramicidins which also form active channels, but of different lifetimes and/or ion transport rates from the native molecules; and (3) a larger protein, one of the type El colicins which have recently been shown to form voltage-dependent sodium/potassium channels in the E. coli membrane and in artificial lipid bilayers. The purpose in studying these type of molecules is to establish principles governing possible modes of action of all such channel-forming proteins in biological systems. The results will indicate the molecular basis for the action of ion pumps and gates in membranes, which in turn directly affect (a) a cell's ability to control its ionic composition, transmembrane potential and osmotic pressure, and (b) the conduction of nerve impulses in higher animals. Our previous work has characterized a conformational change which accompanies cation binding to gramicidins A, B, and C. A combination of neutron diffraction and x-ray diffraction are being used to further examine these structures, including the use of isomorphous deuterium-hydrogen substitution to phase reflections in single-crystal neutron diffraction. In addition, the conducting properties of a variety of semisynthetic gramicidin A analogues, in which amino acids having side chains of varying size and polarity have been substituted at the N-terminal, are being examined.