A survey of integral α-helical membrane proteins
A survey of integral α-helical membrane proteins
复制标题
DOI：
10.1007/s10969-009-9069-8
复制
发表时间：
2009-12-01
期刊：
影响因子：
--
通讯作者：
Sali, Andrej
中科院分区：
文献类型：
--
作者：
Kelly, Libusha;Pieper, Ursula;Sali, Andrej
膜蛋白充当细胞的看门人、调节器和传感器。先前的研究已经探索了特别感兴趣的蛋白质和家族的功能广度和进化，例如原核生物和真核生物中转运相关膜蛋白家族的多样性，完整膜蛋白的组成，以及所有人类G蛋白偶联受体的家族分类。然而，一个全面的分析的内容和进化之间的关联膜蛋白和家庭在不同的基因组是缺乏的。在这里，开发了一个膜蛋白注释管道来定义完整的膜基因组和来自34个基因组的21，379个蛋白质之间的关联;大多数但不是所有这些蛋白质属于598个定义的家族。该管道用于为结构基因组学项目提供目标输入，该项目成功地克隆，表达和纯化了我们在酵母中选择的前96个目标中的61个。此外，该方法被应用于（1）探索人类ABC转运蛋白超家族的底物结合跨膜结构域的进化历史，（2）鉴定全基因组中的多药耐药相关膜蛋白，以及（3）鉴定推定的新膜蛋白家族。
Membrane proteins serve as cellular gatekeepers, regulators, and sensors. Prior studies have explored the functional breadth and evolution of proteins and families of particular interest, such as the diversity of transport-associated membrane protein families in prokaryotes and eukaryotes, the composition of integral membrane proteins, and family classification of all human G-protein coupled receptors. However, a comprehensive analysis of the content and evolutionary associations between membrane proteins and families in a diverse set of genomes is lacking. Here, a membrane protein annotation pipeline was developed to define the integral membrane genome and associations between 21,379 proteins from 34 genomes; most, but not all of these proteins belong to 598 defined families. The pipeline was used to provide target input for a structural genomics project that successfully cloned, expressed, and purified 61 of our first 96 selected targets in yeast. Furthermore, the methodology was applied (1) to explore the evolutionary history of the substrate-binding transmembrane domains of the human ABC transporter superfamily, (2) to identify the multidrug resistance-associated membrane proteins in whole genomes, and (3) to identify putative new membrane protein families.