Conformations of c-type cytochrome self-assembling complexes

描述(由申请人提供)：电子转移(ET)反应对包括光合作用和呼吸作用在内的广泛的生物重要过程至关重要。在光合作用和呼吸作用中，ET反应需要蛋白质的有组织的组装。我们的长期目标是确定蛋白质构象在ET中的作用。这就需要构建和研究具有内质网能力的超分子组装模型。我们的假设是，C型细胞色素将提供这样一个模型系统。我们基于三个观察：(1)它们参与几乎所有生物体的呼吸过程，(2)一些可以自组装成链，(3)当它们与某些小分子结合时，它们能够进行电子转移。多结构域c-细胞色素作为元件应用于仿生储能装置中，如电线或催化部位。关于这些超分子结构的详细结构信息将有助于深入了解构象在ET反应中的作用及其作为ET试剂的适用性。为了在生物环境(水溶液)中解析这些配合物的结构，采用了广角X射线散射技术。然而，这项技术需要构建分子模型来解释实验数据。因此，提出的工作的具体目标是利用分子动力学来创建这样的模型，计算它们的X射线散射模式，并通过与实验数据的比较，提供C型细胞色素络合物的原子水平图像。在这个试点项目中，我们将：(1)通过溶液相分子动力学计算以及计算和实验散射数据的比较，通过构建构象模型来阐明细胞色素C7的二、三和四异构体的结构；(2)获得足够的数据，以便提交SC1类型的建议。这项工作的成功完成将阐明构象在内质网中的作用以及细胞色素C7复合体作为能量存储设备的构建块的适用性。 与公共健康相关：目前的研究重点是评估一种被提议作为新的太阳能存储设备的自组装系统。更高效的太阳能系统将减少化石燃料的使用，因为化石燃料对空气污染的贡献与日益严重的呼吸系统疾病有关。

DESCRIPTION (provided by applicant): Electron transfer (ET) reactions are crucial for a wide range of biologically important processes including photosynthesis and respiration. In photosynthesis and respiration, ET reactions require an organized assembly of proteins. Our long-term goal is to determine the role of protein conformation on ET. This requires the construction and investigation of model supramolecular assemblies capable of ET. Our hypothesis is that c-type cytochromes will provide such a model system. We base this hypothesis on three observations: (1) they are involved in the respiratory processes of almost all organisms, (2) some can self-assemble into chains, and (3) they are capable of electron transfer when bound to certain small molecules. Multi-domain c-cytochromes have applications as components in bio-mimetic energy storage devices as electric wires or catalytic sites. Detailed structural information about these supramolecular architectures would provide insight into the role of conformation in ET reactions and their suitability as ET agents. To resolve the structure of these complexes in their biological environment (aqueous solutions) wide-angle X-ray scattering techniques are employed. However, this technique requires the construction of molecular models to interpret the experimental data. Hence, the specific goal of the proposed work is to use molecular dynamics to create such models, calculate their X-ray scattering patterns, and by comparison to the experimental data, provide an atomic level picture of c-type cytochrome complexes. In this pilot project, we will: (1) elucidate the structure of di-, tri-, and tetramers of cytochrome c7 by construction of conformation models via solution phase molecular dynamics calculations and comparison of the calculated and experimental scattering data; (2) acquire sufficient data to allow submission of a SC1-type proposal. Successful completion of this work will illuminate the role of conformation in ET and the suitability of cytochrome c7 complexes as building blocks for energy storage devices. Relevance to Public Health: The current study focuses on evaluating a self-assembling system that has been proposed as a new solar energy storage device. More efficient solar energy systems would allow a reduction in fossil fuel usage which, due to its contribution to air pollution, has been linked to increasing respiratory disorders.