Studies on Protein Lipidation

蛋白质脂化研究

• 批准号: 9707092
• 负责人: Howard C Hang
• 金额: $ 7.87万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9707092
• 关键词: Acyltransferase; Address; Alkynes; Animal Model; Antiviral Agents; Applications Grants; Bacteria; Biochemical; Bioinformatics; Biological; Biological Assay; Biology; Cell Line; Cells; Cellular biology; Chemicals; Complex; Cysteine; Dendritic Cells; Detection; Eukaryota; Fatty Acids; Genomics; Goals; Grant; Host Defense; Host resistance; Human; Immunity; In Vitro; Infection; Influenza A virus; Integral Membrane Protein; Integration Host Factors; Interferons; Label; Laboratories; Life; Ligation; Lipids; Mammalian Cell; Membrane; Metabolic; Methods; Mus; Palmitic Acids; Pathway interactions; Phenotype; Protein Analysis; Protein Biochemistry; Protein Isoforms; Protein S; Proteins; Proteomics; Reagent; Reporter; Resistance; Role; Series; Signal Pathway; Site; Virus Diseases; Yeasts; base; biophysical analysis; cell type; combat; esterase; fatty acylation; influenzavirus; microbial; mutant; novel; palmitoylation; predictive tools; reconstitution; tool

PROJECT SUMMARY Lipid chemical reporters and bioorthogonal ligation methods developed by my laboratory have provided new opportunities to investigate the functions of lipid-modified proteins in biology. Our proteomic analysis of fatty- acylated proteins in dendritic cells using fatty acid chemical reporters and bioorthogonal chemical proteomics has revealed a new role for protein S-fatty-acylation in host defense against viral infections. We discovered that S-fatty-acylation of membrane-proximal cysteines on murine IFITM3 is crucial for its membrane localization and antiviral activity against influenza A virus. The mechanisms that control S-fatty-acylation of human IFITM proteins have not been evaluated and will be addressed in this grant proposal. Aim 1 will evaluate the S-fatty-acylation levels, sites and function of human IFITM isoforms in different cell types/states of activation. Aim 2 describes the characterization of fatty acids covalently attached to human IFITM3 in cells. Aim 3 describes site-specific lipidation and reconstitution of IFITM3 in vitro for detailed biochemical and biophysical studies. Determining the mechanisms that control S-fatty-acylation IFITM3 function is crucial for understanding host immunity and may reveal new strategies for combatting virus infection in humans. The chemical approaches described in this grant should provide new reagents and methods for studying fatty- acylated proteins.

项目总结