Transcriptional Regulation and Biochemistry Unit, Metabolism Branch, National Cancer Institute, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA.
J Cell Sci. 2010 Jan 15;123(Pt 2):159-63. doi: 10.1242/jcs.057216.
The regulation of transcription and of many other cellular processes involves large multi-subunit protein complexes. In the context of transcription, it is known that these complexes serve as regulatory platforms that connect activator DNA-binding proteins to a target promoter. However, there is still a lack of understanding regarding the function of these complexes. Why do multi-subunit complexes exist? What is the molecular basis of the function of their constituent subunits, and how are these subunits organized within a complex? What is the reason for physical connections between certain subunits and not others? In this article, I address these issues through a model of network allostery and its application to the eukaryotic RNA polymerase II Mediator transcription complex. The multiple allosteric networks model (MANM) suggests that protein complexes such as Mediator exist not only as physical but also as functional networks of interconnected proteins through which information is transferred from subunit to subunit by the propagation of an allosteric state known as conformational spread. Additionally, there are multiple distinct sub-networks within the Mediator complex that can be defined by their connections to different subunits; these sub-networks have discrete functions that are activated when specific subunits interact with other activator proteins.
转录和许多其他细胞过程的调节涉及到大型多亚基蛋白复合物。在转录的背景下，人们已经知道这些复合物作为调节平台，将激活剂 DNA 结合蛋白连接到靶启动子上。然而，对于这些复合物的功能，我们仍然缺乏了解。多亚基复合物为什么存在？它们组成亚基的功能的分子基础是什么，这些亚基在复合物中是如何组织的？为什么某些亚基之间存在物理连接而不是其他亚基之间存在物理连接？在本文中，我通过网络变构的模型及其在真核 RNA 聚合酶 II 中介转录复合物中的应用来解决这些问题。多变构网络模型（MANM）表明，中介等蛋白复合物不仅作为物理实体存在，而且作为相互连接的蛋白功能网络存在，信息通过一种称为构象扩展的变构状态从亚基传递到亚基。此外，中介复合物内还有多个不同的子网络，可以通过它们与不同亚基的连接来定义；这些子网络具有离散的功能，当特定亚基与其他激活蛋白相互作用时，这些功能就会被激活。
