Collins M O, Grant S G N
Proteomic Mass Spectrometry, The Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom.
Subcell Biochem. 2007;43:185-207. doi: 10.1007/978-1-4020-5943-8_9.
It is now apparent that multiprotein signalling complexes or "signalling machines" are responsible for orchestrating many complex signalling pathways in the cell. The synapse is a sub-cellular specialisation which transmits and converts patterns of electrical activity into cellular memory. This processing of electrical information is mediated by the protein components of the synapse. The organisation of synaptic proteins has been investigated over the last number of years using proteomic methods and with the application ofbioinformatics; a landscape of modular protein complexes at the synapse is emerging. Many share a common organisation centred on a receptor/channel, a protein scaffold, (in which the signalling molecules are localised) and membrane to cytoskeleton interactions. The use of PDZ-domain based protein scaffolds is a particularly common feature in the construction of neuronal protein complexes and the differential presence of these proteins in complexes can have functional consequences. Here we overview current proteomic methodologies for the analysis of multiprotein complexes. In addition, we describe the characterisation of a number of multiprotein complexes associated with ion channels (NMDAR, P2X7 and Kir2) and GPCRs (5-HT2A/5-HT2C, D2 and mGluR5) and discuss common their common components and organisation.
现在很明显，多蛋白信号复合物或“信号机器”负责协调细胞内许多复杂的信号通路。突触是一种亚细胞特化结构，它将电活动模式进行传递并转化为细胞记忆。这种电信息的处理是由突触的蛋白质成分介导的。在过去几年中，人们利用蛋白质组学方法并结合生物信息学对突触蛋白的组织进行了研究；突触处模块化蛋白复合物的全貌正在显现。许多复合物都有一个共同的组织架构，其核心是受体/通道、蛋白质支架（信号分子定位于其中）以及膜与细胞骨架的相互作用。基于PDZ结构域的蛋白质支架的使用是构建神经元蛋白复合物的一个特别常见的特征，这些蛋白质在复合物中的差异存在可能会产生功能影响。在这里，我们概述了用于分析多蛋白复合物的当前蛋白质组学方法。此外，我们描述了一些与离子通道（NMDAR、P2X7和Kir2）和G蛋白偶联受体（5-HT2A/5-HT2C、D2和mGluR5）相关的多蛋白复合物的特征，并讨论了它们的共同成分和组织架构。
