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: 8504116
• 负责人: David M. Engman
• 金额: $ 38.15万
• 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 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8504116
• 关键词: 2-bromopalmitate; 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; 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; public health relevance; 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.

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