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首页> 外文期刊>Chemistry: A European journal >Protein conformational switches: From nature to design
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Protein conformational switches: From nature to design

机译：蛋白质构象转换：从自然到设计

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Protein conformational switches alter their shape upon receiving an input signal, such as ligand binding, chemical modification, or change in environment. The apparent simplicity of this transformation which can be carried out by a molecule as small as a thousand atoms or so belies its critical importance to the life of the cell as well as its capacity for engineering by humans. In the realm of molecular switches, proteins are unique because they are capable of performing a variety of biological functions. Switchable proteins are therefore of high interest to the fields of biology, biotechnology, and medicine. These molecules are beginning to be exploited as the core machinery behind a new generation of biosensors, functionally regulated enzymes, and "smart" biomaterials that react to their surroundings. As inspirations for these designs, researchers continue to analyze existing examples of allosteric proteins. Recent years have also witnessed the development of new methodologies for introducing conformational change into proteins that previously had none. Herein we review examples of both natural and engineered protein switches in the context of four basic modes of conformational change: rigid-body domain movement, limited structural rearrangement, global fold switching, and folding-unfolding. Our purpose is to highlight examples that can potentially serve as platforms for the design of custom switches. Accordingly, we focus on inducible conformational changes that are substantial enough to produce a functional response (e.g., in a second protein to which it is fused), yet are relatively simple, structurally well-characterized, and amenable to protein engineering efforts.
机译：蛋白质构象开关在收到输入信号（例如配体结合，化学修饰或环境变化）时会改变其形状。这种转化可以由一个小至一千个原子左右的分子完成，这种表面上的简单性掩盖了它对细胞生命及其对人类工程改造的能力的至关重要性。在分子开关领域，蛋白质是独一无二的，因为它们能够执行多种生物学功能。因此，可转换蛋白质在生物学，生物技术和医学领域具有很高的兴趣。这些分子已开始被用作新一代生物传感器，功能受控的酶和对周围环境做出反应的“智能”生物材料背后的核心机制。作为这些设计的灵感，研究人员继续分析现有的变构蛋白实例。近年来，还见证了将构象变化引入到以前没有的蛋白质中的新方法的发展。本文中，我们在构象变化的四种基本模式下回顾了天然和工程蛋白转换的例子：刚体结构域运动，有限的结构重排，整体折叠转换和折叠展开。我们的目的是强调一些示例，这些示例可以用作设计自定义交换机的平台。因此，我们集中于可诱导的构象变化，该构象变化足以产生功能性反应（例如，在与之融合的第二种蛋白质中），但是相对简单，结构良好地表征并且适合蛋白质工程的努力。

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