MECHANISM OF ION TRANSPORT THROUGH MEMBRANE CHANNELS

这项研究的目的是了解钠的化学基础 和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处理： 作为二聚体结合形成跨膜通道的cidin A、B和C;（2） 各种化学修饰的类似物，包括共价偶联的同源和 异二聚体，这些同样的短杆菌肽，也形成活性通道，但 与天然分子不同的寿命和/或离子传输速率;以及 (3)一种更大的蛋白质，最近被证明是El型大肠杆菌素之一， 在E.大肠杆菌膜和 在人造脂质双层中。 研究这类分子的目的 是建立指导所有这些行动的可能模式的原则， 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， （B）神经传导 高等动物的冲动 我们以前的工作已经描述了伴随着 阳离子结合短杆菌肽A、B和C。 中子衍射 并且X射线衍射被用于进一步检查这些结构， 包括使用同晶氘-氢取代物来相 单晶中子衍射中的反射。 此外， 各种半合成短杆菌肽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经在 N-末端，正在被检查。

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.