Department of Biochemistry, The Donnelly Centre, University of Toronto, Toronto, ON, Canada.
Curr Opin Nephrol Hypertens. 2011 Jul;20(4):425-32. doi: 10.1097/MNH.0b013e3283478611.
Many cellular processes are controlled via either stable or transient protein-protein interactions (PPIs). Protein complexes are 'molecular machines' in which multiple interactive partners carry out various cellular functions. Given that almost a third of the proteome consists of membrane proteins and that more than 50% of currently available drugs are targeted toward them, investigation of membrane protein complexes has taken center stage over the past years. Thus, gaining an in-depth understanding of PPI networks will give us more insight into the functional relationship as well as downstream effectors of protein complexes, hence opening strategies for new drug target definitions.
Studying membrane proteins in yeast has recently been applied to many different classes of proteins with diverse functions and structures including membrane transporters. Techniques such as the split-ubiquitin membrane yeast two-hybrid or variants of the protein-fragment complementation assay have been successfully applied to both large-scale genome-wide screens and as smaller-scale PPI studies in a reliable and robust fashion.
Yeast-based methods to study membrane PPI in vivo offer a powerful tool for the investigation of protein complexes from various organisms, including mammals. The investigation of global protein maps will serve as a foundation for mechanistic and quantitative studies of poorly characterized gene products and disease-associated proteins. Identification of PPIs is also of great interest for drug discovery as many human diseases result from abnormal PPIs.
许多细胞过程通过稳定或瞬时的蛋白质-蛋白质相互作用（PPIs）来控制。蛋白质复合物是“分子机器”，其中多个相互作用的伴侣执行各种细胞功能。鉴于蛋白质组的近三分之一由膜蛋白组成，并且目前可用的 50%以上的药物针对它们，因此近年来对膜蛋白复合物的研究已经成为焦点。因此，深入了解 PPI 网络将使我们更深入地了解蛋白质复合物的功能关系以及下游效应物，从而为新的药物靶点定义开辟策略。
最近，在酵母中研究膜蛋白已应用于许多具有不同功能和结构的不同类别的蛋白质，包括膜转运蛋白。分裂泛素膜酵母双杂交或蛋白片段互补测定的变体等技术已成功应用于大规模全基因组筛选以及更小规模的 PPI 研究，具有可靠和稳健的方式。
基于酵母的体内研究膜 PPI 的方法为研究来自各种生物体（包括哺乳动物）的蛋白质复合物提供了有力的工具。对全局蛋白质图谱的研究将作为对机制和定量研究的基础，这些研究针对的是特征描述较差的基因产物和与疾病相关的蛋白质。鉴定 PPI 对于药物发现也很有意义，因为许多人类疾病是由异常的 PPI 引起的。
