Hawkins A R, Lamb H K
Department of Biochemistry and Genetics, Medical School, University of Newcastle upon Tyne, England.
Eur J Biochem. 1995 Aug 15;232(1):7-18. doi: 10.1111/j.1432-1033.1995.tb20775.x.
The aim of this review is to give an overview of the contribution molecular biology can make to an understanding of the functions and interactions within multidomain proteins. The contemporary advantages ascribed to multidomain proteins include (a) the potential for metabolite channelling and the protection of unstable intermediates; (b) the potential for interactions between domains catalysing sequential steps in a metabolic pathway, thereby giving the potential for allosteric interactions; and (c) the facility to produce enzymic activities in a fixed stoichiometric ratio. The alleged advantages in (a) and (b) however apply equally well to multi-enzyme complexes; therefore, specific examples of these phenomena are examined in multidomain proteins to determine whether the proposed advantages are apparent. Some transcription-regulating proteins active in the control of metabolic pathways are composed of multiple domains and their control is exerted and modulated at the molecular level by protein-DNA, protein-protein and protein-metabolite interactions. These complex recognition events place strong constraints upon the proteins involved, requiring the recognition of and interaction with different classes of cellular metabolites and macromolecules. Specific examples of transcription-regulating proteins are examined to probe how their multidomain nature facilitates a general solution to the problem of multiple recognition events. A general unifying theme that emerges from these case studies is that a basic unitary design of modules provided by enzymes is exploited to produce multidomain proteins by a complex series of gene duplication and fusion events. Successful modules provided by enzymes are co-opted to new function by selection apparently acting upon duplicated copies of the genes encoding the enzymes. In multidomain transcription-regulating proteins, former enzyme modules can be recruited as molecular sensors that facilitate presumed allosteric interactions necessary for the molecular control of transcription.
本综述的目的是概述分子生物学在理解多结构域蛋白的功能及相互作用方面所能做出的贡献。多结构域蛋白目前被认为具有的优势包括：（a）代谢物通道化以及保护不稳定中间体的潜力；（b）催化代谢途径中连续步骤的结构域之间相互作用的潜力，从而产生变构相互作用的可能性；（c）以固定化学计量比产生酶活性的便利。然而，（a）和（b）中所谓的优势同样适用于多酶复合物；因此，本文研究了多结构域蛋白中这些现象的具体实例，以确定所提出的优势是否明显。一些在代谢途径控制中起作用的转录调节蛋白由多个结构域组成，它们的控制在分子水平上通过蛋白质 - DNA、蛋白质 - 蛋白质和蛋白质 - 代谢物相互作用来施加和调节。这些复杂的识别事件对相关蛋白质施加了严格限制，要求识别并与不同类型的细胞代谢物和大分子相互作用。本文研究了转录调节蛋白的具体实例，以探究其多结构域性质如何有助于找到解决多重识别事件问题的通用方法。这些案例研究中出现的一个普遍统一主题是，酶提供的模块的基本单一设计通过一系列复杂的基因复制和融合事件被用于产生多结构域蛋白。显然，通过对编码酶的基因的重复拷贝进行选择，酶提供的成功模块被赋予了新功能。在多结构域转录调节蛋白中，以前的酶模块可以被招募为分子传感器，促进转录分子控制所需的假定变构相互作用。
