Global Characterization of Protein Palmitoylation in Trypanosomes

棕榈酰化是一种蛋白质的翻译后修饰，可以影响蛋白质如何与膜室中的脂质和蛋白质相互作用。双氨基酰化与肉豆蔻酸酯和棕榈酸酯是必不可少的靶向蛋白质脂筏，是一种常见的

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.