Visualization and assessment of physical and chemical interactions among smooth muscle proteins

本研究项目引入了一种创新的技术，通过结合蛋白质生物化学和分子成像来研究蛋白质相互作用的每一步。这项技术对于理解蛋白质相互作用至关重要，因为蛋白质相互作用严重依赖于蛋白质聚集体的结构（例如，当聚集体的结构是决定聚集体化学性质的一个因素时）。这项技术的一个很好的应用是研究肌凝蛋白和肌动蛋白（肌肉细胞中负责产生力量和运动的主要蛋白质）在肌肉收缩中的相互作用。肌凝蛋白和肌动蛋白都以丝状形式存在于肌肉细胞中，这是由于蛋白质的聚合，丝状肌凝蛋白和丝状肌动蛋白的相互作用发生在细胞中，而不是单个肌凝蛋白和肌动蛋白分子之间的相互作用。因此，可视化反应中涉及的元素是至关重要的。该研究项目的另一个重点是旨在阐明平滑肌收缩的基本机制（平滑肌是一种在胃、膀胱、血管和气道等中空器官中发现的肌肉类型，控制着重要器官的功能）。与骨骼肌或心肌相比，我们对平滑肌的工作原理知之甚少。我们建议使用纯化的平滑肌收缩蛋白作为构建块来构建平滑肌的基本收缩单元。这将使我们了解可收缩单元的分子成分及其工作原理。该研究计划将对我们对平滑肌基本细胞生理学的理解和新技术的发展产生重大影响，该技术可用于许多研究领域，以寻求理解纳米颗粒或分子之间相互作用的本质，特别是当颗粒或分子聚集体的结构（或构象）是一个重要的考虑因素时。

This research program introduces an innovative technique of studying interactions of proteins by combining protein biochemistry and molecular imaging at every step of the interaction. This technique is crucial for understanding protein interactions that critically depends on the structure of the protein aggregate (e.g., when the structure of the aggregate is a factor determining the chemical properties of the aggregate). A good application of this technique is in the study of the interaction of myosin and actin (major proteins responsible for generating force and movement in muscle cells) in muscle contraction. Both myosin and actin exist in muscle cells in filamentous forms due to polymerization of the proteins and it is the interaction of filamentous myosin and filamentous actin that occurs in the cell and not the interaction between individual myosin and actin molecules. It is therefore crucial to visualize the elements involved in the reaction. Another focus of this research program is aimed at elucidating the basic mechanism of contraction in smooth muscle (the type of muscle found in hollow organs like stomach, urinary bladder, blood vessels and airways that controls vital organ functions). Compared to skeletal or heart muscles, we know very little about how smooth muscle works. We propose to construct the basic contractile unit in smooth muscle using purified smooth muscle contractile proteins as building blocks. This will allow us to understand the molecular constituents of the contractile unit and how it works. The research program will have great impacts on both our understanding of basic cell physiology of smooth muscle and the development of a novel technique that can be used in many fields of research that seek to understand the nature of interaction between nano-particles or molecules, especially when the structure (or conformation) of the particle or molecular aggregates is an important consideration.