Hu Zhang-Zhi, Valencia Julio C, Huang Hongzhan, Chi An, Shabanowitz Jeffrey, Hearing Vincent J, Appella Ettore, Wu Cathy
Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC.
Int J Mass Spectrom. 2007 Jan 1;259(1-3):147-160. doi: 10.1016/j.ijms.2006.09.024.
Complete and accurate profiling of cellular organelle proteomes, while challenging, is important for the understanding of detailed cellular processes at the organelle level. Mass spectrometry technologies coupled with bioinformatics analysis provide an effective approach for protein identification and functional interpretation of organelle proteomes. In this study, we have compiled human organelle reference datasets from large-scale proteomic studies and protein databases for 7 lysosome-related organelles (LROs), as well as the endoplasmic reticulum and mitochondria, for comparative organelle proteome analysis. Heterogeneous sources of human organelle proteins and rodent homologs are mapped to human UniProtKB protein entries based on ID and/or peptide mappings, followed by functional annotation and categorization using the iProXpress proteomic expression analysis system. Cataloging organelle proteomes allows close examination of both shared and unique proteins among various LROs and reveals their functional relevance. The proteomic comparisons show that LROs are a closely related family of organelles. The shared proteins indicate the dynamic and hybrid nature of LROs, while the unique transmembrane proteins may represent additional candidate marker proteins for LROs. This comparative analysis, therefore, provides a basis for hypothesis formulation and experimental validation of organelle proteins and their functional roles.
完整而准确地描绘细胞器蛋白质组,虽然具有挑战性,但对于在细胞器水平上理解详细的细胞过程非常重要。质谱技术与生物信息学分析相结合,为细胞器蛋白质组的蛋白质鉴定和功能解读提供了一种有效方法。在本研究中,我们从大规模蛋白质组学研究和蛋白质数据库中收集了7种溶酶体相关细胞器(LRO)以及内质网和线粒体的人类细胞器参考数据集,用于细胞器蛋白质组的比较分析。人类细胞器蛋白质和啮齿动物同源物的异质来源基于ID和/或肽映射映射到人类UniProtKB蛋白质条目,随后使用iProXpress蛋白质组表达分析系统进行功能注释和分类。对细胞器蛋白质组进行编目可以仔细研究各种LRO之间共享和独特的蛋白质,并揭示它们的功能相关性。蛋白质组学比较表明,LRO是一个密切相关的细胞器家族。共享蛋白质表明LRO的动态和混合性质,而独特的跨膜蛋白质可能代表LRO的额外候选标记蛋白。因此,这种比较分析为细胞器蛋白质及其功能作用的假设形成和实验验证提供了基础。