Global Characterization of Protein Palmitoylation in Trypanosomes

锥虫中蛋白质棕榈酰化的整体表征

• 批准号: 8829304
• 负责人: David M. Engman
• 金额: $ 36.54万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8829304
• 关键词: APPBP2 gene; Acylation; Acyltransferase; Affect; African; African Trypanosomiasis; Algorithms; Aminoacylation; Animal Model; Animals; Biological Models; Biology; Blood Circulation; Calcium-Binding Proteins; Cell physiology; Cells; Cellular Structures; Chagas Disease; Chemistry; Complex; Cutaneous Leishmaniasis; Data; Disease; Drug Targeting; Endoplasmic Reticulum; Enzymes; Eukaryota; Eukaryotic Cell; Genes; Genetic; Goals; Growth; Health; In Vitro; Individual; Infection; Insecta; Knock-out; Leishmania; Light; Link; Lipids; Location; Maps; Mediating; Membrane; Membrane Microdomains; Modification; Mucocutaneous leishmaniasis; Myristates; N-Myristoylation; N-myristoyltransferase; N-terminal; Nature; Organism; Palmitates; Palmitic Acylation Site; Parasites; Peptides; Pharmaceutical Preparations; Post-Translational Protein Processing; Process; Protein Analysis; Proteins; Proteome; Qualifying; RNA Interference; Research; Risk; Signal Transduction; Signaling Molecule; Staging; Substrate Specificity; System; Time; Toxic effect; Transferase; Trypanosoma; Trypanosoma brucei brucei; Trypanosoma cruzi; Vaccines; Validation; Vesicle; Virulence; Virulence Factors; Visceral Leishmaniasis; Work; chemotherapy; homologous recombination; in vivo; interest; member; neglect; novel; palmitoylation; pathogen; prevent; tool

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.

描述（由申请方提供）：锥虫中蛋白质棕榈酰化的总体表征棕榈酰化是一种蛋白质的翻译后修饰，可影响蛋白质如何与膜隔室中的脂质和蛋白质相互作用。肉豆蔻酸酯和棕榈酸酯的双重氨酰化对于蛋白质靶向脂筏是必需的，并且是常见的 细胞信号传导中关键分子的特征。虽然N-肉豆蔻酰化在内质网中通过单个N-肉豆蔻酰转移酶进行，但S-棕榈酰化和很少的N-棕榈酰化（发生在N-末端半胱氨酸残基上）由许多棕榈酰酰基转移酶（PAT）中的一种介导，每种具有其自身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， 真核生物因此，鉴定和连接特定的PAT及其底物构成了系统分析真核生物生物学的独特方法。在非洲锥虫，布氏锥虫，我们的LC-MS/MS和RNAi数据强烈表明，蛋白质棕榈酰化是一个丰富的和重要的修改。在这个项目中，我们将对T. brucei在一个为期五年的密集的研究工作，将确定棕榈酰蛋白质组的T。brucei，确定T.布氏杆菌PAT，并研究这类酶作为杀锥虫化疗的潜在靶点。