Protein conformational switches: from nature to design.
Protein conformational switches: from nature to design.
复制标题
蛋白质构象转换：从自然到设计。
DOI：
10.1002/chem.201200348
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发表时间：
2012-06-25
影响因子：
4.3
通讯作者：
Loh, Stewart N.
中科院分区：
文献类型：
--
作者：
Ha, Jeung-Hoi;Loh, Stewart N.
蛋白质构象开关在接收到输入信号时改变其形状，例如配体结合、化学修饰或环境变化。这种转化表面上看起来很简单--它可以由一个小到一千个原子的分子来完成--掩盖了它对细胞生命的重要性，以及它的人类工程能力。在分子开关领域，蛋白质是独一无二的，因为它们能够执行各种生物功能。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。这些分子开始被开发为新一代生物传感器、功能调节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的例子。近年来，人们还发现了一些新的方法，可以将构象变化引入到以前没有构象变化的蛋白质中。在这里，我们回顾了自然和工程蛋白开关的例子中的四个基本模式的构象变化：刚体结构域运动，有限的结构重排，全球折叠开关，折叠展开。我们的目的是突出的例子，可以作为平台的定制开关的设计。因此，我们专注于诱导型构象变化，这些变化足以产生功能性反应（例如，在与其融合的第二种蛋白质中），但相对简单，结构特征良好，并适合于蛋白质工程的努力。
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, bio-technology, 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.
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影响因子：
2.9
作者：
Bermejo, Guillermo A.;Strub, Marie-Paule;Ho, Chien;Tjandra, Nico
通讯作者：
Tjandra, Nico
影响因子：
5.6
作者：
Alicea I;Marvin JS;Miklos AE;Ellington AD;Looger LL;Schreiter ER
通讯作者：
Schreiter ER
DOI：
10.1073/pnas.0509349102
发表时间：
2005-12-20
影响因子：
11.1
作者：
Anderson, TA;Cordes, MHJ;Sauer, RT
通讯作者：
Sauer, RT
影响因子：
4
作者：
Borrok, M. Jack;Zhu, Yimin;Forest, Katrina T.;Kiessling, Laura L.
通讯作者：
Kiessling, Laura L.
影响因子：
2.9
作者：
Cheng, Guilong;Cusanovich, Michael A.;Wysocki, Vicki H.
通讯作者：
Wysocki, Vicki H.