後基因體時代的一個主要的挑戰就是研究細胞中全部表達出來的蛋白質—也就是蛋白體。轉譯後之修飾使蛋白質的複雜度提昇,不只僅是二十個氨基酸之排列組合而已。本計劃就是要用蛋白體的研究方法來分析一種轉譯後的修飾—蛋白質精胺酸甲基化,主要為使用蛋白質體的方法二維電泳後以質譜來分析。我們也已成功的找到一些已知的甲基接受蛋白和某些可能的新甲基接受蛋白。此計劃我們致力於以下四個方向: (一)蛋白質體法整體性的分析甲基接受蛋白。 (二)分析所有蛋白質精胺酸甲基脢在生物界中存在情形。 (三)探討透過上述的方法找出之新甲基接受蛋白質的特性。 (四)我們將藉由蛋白質體的研究方法法來分析不同生物醫學樣本的精胺酸甲基接受蛋白,以找出蛋白質精胺酸甲基化和人類特殊疾病主要為自體免疫疾病之間的相關性。透過這些蛋白質體的研究我們將可明確得知甲基接受蛋白精胺酸甲基化的功能,使我們能更加暸解此種轉譯後修飾所扮演的的角色。
In the post-genomic era the major challenge is to investigate the complete expressed proteins in cells, the proteome. Posttranslational modifications increase the complexity of proteins beyond the combination of twenty amino acids. The project will investigate one type of protein posttranslational modification— protein arginine methylation using the proteomic tools, basically two dimensional gel electrophoresis followed by mass spectrometry to identify specific protein spot. We have started the investigation of the methylaccepting proteins using proteomic approach and successfully identified some known and novel putative methylaccepting proteins. In this project we focus on four areas. Firstly, we perform global analysis of protein methylaccepting proteins by the proteomic approach. Secondly, we analyze protein arginine methylacceptors globally in subcellular localization. Thirdly, we characterize the novel protein methyl- acceptors identified through the above approaches. At last, we analyze the relationship of protein arginine methyl- -ation with specific human diseases by proteomic analyses of the arginine methylaccepting proteins in different biomedical samples. Through these studies we will identify, and specify the function of arginine methylation of the methylaccepting proteins through the proteomic approach, to help to better understand the roles of this posttranslational modification.