Global Characterization of Protein Palmitoylation in Trypanosomes

描述(申请人提供)：锥虫体内蛋白质棕榈酰化的全球特征：棕榈酰化是蛋白质的翻译后修饰，可以影响蛋白质如何与膜室中的脂类和蛋白质相互作用。与肉豆蔻酸酯和棕榈酸酯的双重氨基酰化是蛋白质靶向脂筏的关键，也是一种常见的 细胞信号中的关键分子的特征。在内质网中，N-肉豆蔻酰化是通过单一的N-肉豆蔻酰化转移酶进行的，而S棕榈酰化作用和很少的N-棕榈酰化作用(发生在N-末端的半胱氨酸残基上)是由许多棕榈酰基转移酶(PATs)中的一种介导的，每种酶都有自己的定位和底物特异性。S-棕榈酰化对于许多重要蛋白质的功能是必不可少的，在 真核生物。因此，鉴定和连接特定的PATS及其底物构成了系统分析真核生物生物学的独特途径。在非洲锥虫中，我们的LC-MS/MS和RNAi数据有力地表明蛋白质棕榈酰化是一种丰富和重要的修饰。在拟议的项目中，我们将在为期五年的密集研究中对布氏毛滴虫的蛋白棕榈酰化进行全球分析，以确定布氏毛滴虫的棕榈酰化蛋白质组，鉴定布氏毛滴虫PATS的底物分布和功能，并研究这类酶作为杀锥虫化疗的潜在靶标。

DESCRIPTION (provided by applicant): Global Characterization of Protein Palmitoylation in Trypanosomes Palmitoylation is a posttranslational modification of proteins that can affect how a protein interacts with lipids and proteins in a membrane compartment. Dual aminoacylation with myristate and palmitate is essential for targeting of proteins to lipid rafts, and is a common feature of key molecules in cell signaling. While N- myristoylation is carried out in the endoplasmic reticulum by a single N-myristoyltransferase, S-palmitoylation, and rarely N-palmitoylation (occurring on an N-terminal cys residue), is mediated by one of a number of palmitoyl acyltransferases (PATs), each having its own localization and substrate specificity. S-palmitoylation is essential for the functions of a number of important proteins and is essential in eukaryotes. Thus, the identification and linkage of specific PATs and their substrates constitutes a unique approach to systematic analysis eukaryote biology. In the African trypanosome, Trypanosoma brucei, our LC-MS/MS and RNAi data strongly suggest that protein palmitoylation is an abundant and important modification. In the proposed project, we will conduct a global analysis of protein palmitoylation in T. brucei in a five-year intensive research effort that will determine the palmitoylproteomes of T. brucei, identify the substrate profiles and functions of T. brucei PATs, and investigate this class of enzymes as potential targets for trypanocidal chemotherapy.