INTERACTIONS OF APO A-I WITH LIPIDS AND CELL SURFACES

APO A-I 与脂质和细胞表面的相互作用

• 批准号: 6296857
• 负责人: Michael C. Phillips
• 金额: $ 27.96万
• 依托单位: MCP HAHNEMANN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-11-11 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6296857
• 关键词: apolipoproteins; blood lipoprotein metabolism; high density lipoproteins; human tissue; hydropathy; intermolecular interaction; laboratory mouse; lipid transport; membrane activity; molecular polarity; molecular shape; molecular size; phospholipids; protein binding; protein engineering; protein structure function; protein transport; receptor; tissue /cell culture

The goal of this project is to elucidate the molecular mechanisms underlying the functions of apolipoprotein (apo) A-I in reverse cholesterol transport (RCT). Apo A-I is the major protein of plasma high density lipoprotein (HDL) and the functions of this molecule underlie the anti-atherogenic properties of this lipoprotein. Specific Aim 1 is to define the domains of apo A-I critical for the binding of phospholipid (PL) and the assembly of various types of HDL particles; this is significant because the ways in which apo A-I participates in RCT depend upon its state of lipidation. The structure-function relationships of apo A-I will be examined using protein molecules altered by mutagenesis. Specific Aim 2 is to define the molecular events involved in the "membrane micro-solubilization" process by which lipid-poor apo A-I (pre-beta-HDL) removes unesterified cholesterol and PL from the plasma membrane of cells. Specific Aim 3 is to elucidate the behavior of apo A-I as a ligand for the scavenger-receptor (SR)-B1 receptor and the molecular mechanism of the selective uptake into cells of cholesteryl ester mediated by the binding of HDL to this receptor. The lipid-binding capabilities of plasma apo A-I, engineered apo A-I and model peptides will be determined using a range of physical-biochemical techniques. The functional domains of apo A-I involved in mediating cholesterol and lipid transport at cell surfaces will be defined by using various engineered apo A-I molecules in cell culture systems. The results of this project will provide greater understanding of the mechanisms by which HDL protects against premature coronary artery disease.

本项目旨在阐明其分子机制