MECHANISM OF ION TRANSPORT THROUGH MEMBRANE CHANNELS

这项拟议研究的目标是了解钠的化学基础。 钾在生物膜上的流动。问题将是 使用细菌来源的三种类型的通道形成分子进行的： 以二聚体形式结合形成跨膜通道的CIDINS A、B和C； 各种化学修饰的类似物，包括共价偶联的同-和 异源二聚体，也形成活性通道，但 天然分子不同的寿命和/或离子传输速率；以及 (3)一种较大的蛋白质，是最近发现的EL结肠素类型之一 在大肠杆菌膜上形成电压依赖的钠/钾通道和 在人工脂双层中。研究这类分子的目的是 是建立管理所有这类人可能采取的行动模式的原则 生物系统中的通道形成蛋白。结果将表明 膜中离子泵和离子门作用的分子基础 反过来直接影响(A)细胞控制其离子组成的能力， 跨膜电位和渗透压，以及(B)神经传导 高等动物的冲动。 我们之前的工作描述了伴随而来的构象变化 阳离子与革兰菌素A、B和C的结合中子衍射法 和X射线衍射被用来进一步研究这些结构， 包括使用同构的重氢取代物相 单晶中子衍射中的反射。此外，指挥 一种半合成的甘草素A类似物的性质，其中氨基 具有不同大小和极性的侧链的酸已被取代 正在对N端子进行检查。

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.