SYNTHETIC RETINAL PIGMENTS AND BINDING PROTEINS

描述(调查人员摘要)：目标是了解 视紫红质发色团对视觉过程的控制 激发和漂白适应。我们的假设是 视紫红质的构象与其产物 漂白、视蛋白和这些构象上的差异会影响 与其他视网膜蛋白的相互作用，进而控制 感光器的灵敏度。生色团的变化 结构允许对生理和生化进行操作 光感受器的。生色团的衍生物，选择用于测试 发色团与发色团相互作用的某些特定方面 蛋白质，将被合成。隔离条件下的生理测量 杆状和圆锥体将与体外测量 所涉及的生化过程。原生的和类比的 颜料将通过各种质谱学和其他方法进行研究 光谱技术和相关的生化发现。两者都有 色素再生的转导过程及其机制 将研究维甲酸终止漂白适应的作用。这个 维甲酸转运和维甲酸结合蛋白的作用将是 由维甲酸类似物检查。对于某些临床情况 视网膜变性，来自几个实验室的数据揭示了 各种视网膜蛋白质的点突变或多态，这 会导致这些蛋白质在视觉上的异常相互作用 转导和适应过程。生色团的衍生物 视紫红质可以诱导视紫红质的异常构象，进而 影响转导过程中与蛋白质的相互作用。这个 这里提出的实验为研究这些临床症状提供了一种手段。 在基本的生化和生理水平上的紊乱。

DESCRIPTION (Investigator's Abstract): The goal is to understand the control of the chromophore of rhodopsin over the processes of visual excitation and bleaching adaptation. The hypothesis is that the rhodopsin has a distinctly different conformation from its product of bleaching, opsin, and these differences in conformation affect the interaction with other retinal proteins that in turn control the sensitivity of the photoreceptor. The change of the chromophore structure allows the manipulation of the physiology and the biochemistry of the photoreceptor. Derivatives of the chromophore, chosen to test some specific aspect of the interaction of the chromophore with the protein, will be synthesized. Physiological measurements in isolated rods and cones will be related to in vitro measurements of the biochemical processes that are involved. The native and analogue pigments will be studied by a variety of mass spectral and other spectroscopic techniques and related to the biochemical findings. Both the transduction process and the mechanisms of pigment regeneration and termination of bleaching adaptation by retinoids will be studied. The role of retinoid transport and the retinoid binding proteins will be examined by retinoid analogues. For certain conditions of clinical retinal degenerations, data from several laboratories reveal the presence of point mutations or polymorphisms in various retinal proteins, which would lead to abnormal interactions of these proteins in the visual transduction and adaptation processes. Derivatives of the chromophore of rhodopsin can induce abnormal conformations of rhodopsin that in turn affect the interaction with proteins in the transduction process. The experiments proposed here offer a means for studying these clinical disorders at the basic biochemical and physiological levels.