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

这项研究计划介绍了一种研究蛋白质相互作用的创新技术，通过在相互作用的每一步结合蛋白质生物化学和分子成像。这项技术对于理解蛋白质相互作用是至关重要的，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因素时)。这项技术的一个很好的应用是研究肌球蛋白和肌动蛋白在肌肉收缩中的相互作用。肌球蛋白和肌动蛋白是肌肉细胞中负责生成力和运动的主要蛋白质。由于蛋白质聚合，肌球蛋白和肌动蛋白都以丝状形式存在于肌肉细胞中，而不是单个肌球蛋白和肌动蛋白分子之间的相互作用，而是肌球蛋白和肌动蛋白在细胞内的相互作用。因此，将反应中涉及的元素形象化是至关重要的。这项研究计划的另一个重点是阐明平滑肌收缩的基本机制(在胃、膀胱、血管和呼吸道等中空器官中发现的控制重要器官功能的肌肉类型)。与骨骼肌或心肌相比，我们对平滑肌肉的工作原理知之甚少。我们建议用纯化的平滑肌收缩蛋白作为基本的收缩单位。这将使我们能够了解收缩单位的分子组成以及它是如何工作的。这项研究计划将对我们理解平滑肌的基本细胞生理学和开发一种新的技术产生重大影响，该技术可用于许多研究领域，试图了解纳米颗粒或分子之间相互作用的性质，特别是当颗粒或分子聚集体的结构(或构象)是一个重要考虑因素时。

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.