课题基金 / 基金详情

Investigation of the Molecular Mechanisms of Lipoprotein Lipase Inhibitors

Investigation of the Molecular Mechanisms of Lipoprotein Lipase Inhibitors
脂蛋白脂肪酶抑制剂的分子机制研究
批准号:
9102237
负责人:
Saskia Neher
金额:
$37.1万
依托单位国家:
美国
项目类别:
财政年份:
2015
资助国家:
美国
项目状态:
已结题
起止时间:
2015-07-01 至 2020-04-30

项目摘要

项目成果

Saskia Neher的其他基金

相关文献

中文摘要
翻译

英文摘要
 DESCRIPTION (provided by applicant): Elevated serum triglycerides are associated with increased risk for cardiovascular disease. Lipoprotein lipase (LPL) is a secreted enzyme that clears lipids from the blood by hydrolyzing the triglycerides component of circulating lipoproteins. LPL has a number of macromolecular inhibitors. In human populations, known mutations in these macromolecular inhibitors result in reduced ability to inhibit LPL. As a result, LPL activity is increased and serum triglycerides are decreased. We recently discovered that one of these proteins, ANGPTL4, acts as a reversible, noncompetitive LPL inhibitor rather than an unfolding molecular chaperone as was previously believed. This new understanding of ANGPTL4 function led us to ask if other LPL inhibitors act on LPL using a similar mechanism. This proposal focuses on biochemically defining the LPL/inhibitor interaction. In Aim 1 we will define the sequence motifs and kinetic and molecular mechanisms used by these inhibitors to reduce LPL activity. In Aim 2, we will identify the features on LPL that are recognized by the inhibitors. In Aim 3 we ask why a variant of LPL has enhanced activity in vivo. To achieve these aims we will combine protein biochemistry, structural proteomics and single molecule TIRF microscopy. Successful completion of these aims will provide a precise molecular understanding of the mechanism of LPL activity and regulation. Because of LPL's key role in human triglyceride metabolism, these discoveries hold promise for developing new therapies for hypertriglyceridemia.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Lipoprotein Lipase Through the Secretory System
Investigation of the Molecular Mechanisms of Lipoprotein Lipase Inhibitors
Investigation of the Molecular Mechanisms of Lipoprotein Lipase Inhibitors
Investigation of the Molecular Mechanisms of Lipoprotein Lipase Inhibitors