Structure and Function of Apolipoproteins

载脂蛋白的结构和功能

• 批准号: 6930446
• 负责人: Jose L. Soulages
• 金额: $ 22.77万
• 依托单位: OKLAHOMA STATE UNIVERSITY STILLWATER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-03-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6930446
• 关键词: apolipoproteins; high density lipoproteins; intermolecular interaction; lipid metabolism; mass spectrometry; protein binding; protein structure function; site directed mutagenesis

DESCRIPTION (provided by applicant): Exchangeable apolipoproteins are essential structural and functional components of lipoproteins. The stability of the lipoprotein particles, the activity of lipolytic enzymes and lipid transfer proteins, and the binding of the lipoprotein to receptors are among the processes regulated by the properties of apolipoproteins, which bind to the lipoprotein lipid surfaces as well as to cell membranes. Apolipoproteins modulate all those 3rocesses by means of their lipid binding activity, rate and extent of binding, and their structure in the lipid-bound state. Therefore, the molecular properties of the exchangeable apolipoproteins define the physiological role of lipoproteins and the homeostasis of the lipid metabolism, in general. The understanding of the physiological role of a given apoLp depends on the knowledge of the structure and properties of the protein molecule in both the soluble and lipid-bound state(s). The long-term goals of this project are the lentification and characterization of the functional domains of apolipoproteins in the lipid-bound states. This proposal involves studies on the relationship between structure and function of two apolipoproteins: insect ,Apolipophorin-Ill and human apolipoprotein A-I. The specific aims of this proposal include: 1) Study of the organization of apoA-I molecules in discoidal HDL iipoproteins; 2) The study of the regions of human apoA-I that interact with lipid in high-density lipoproteins; 3) The study of the correlation between the structure of apoA-I in HDL particles and the function of the lipoproteins. 4) The study of the mechanism of association of apolipophorin-III with phospholipid monolayers and bilayers, including native lipoproteins and reconstituted model lipoproteins; Accomplishment of these objectives is necessary to fully understand the physiology and pathology of the metabolic pathways where apolipoproteins are involved. This includes understanding of the role of apolipoproteins in the metabolism of lipids and related pathologies, such as atherosclerosis, but it could also involve other kind of pathologies, such as Alzheimer's disease.

描述（由申请人提供）：可交换的载脂蛋白是脂蛋白的基本结构和功能成分。脂蛋白颗粒的稳定性，脂肪酶和脂质转移蛋白的活性以及脂蛋白与受体与受体的结合是由载脂蛋白的特性调节的过程之一，这些过程与脂蛋白脂质表面结合，以及与细胞膜以及与脂蛋白脂质表面的结合。载脂蛋白通过其脂质结合活性，结合速率和结合及其在脂质结合状态下的结构来调节所有这些3过程。因此，一般而言，可交换载脂蛋白的分子特性定义了脂蛋白和脂质代谢的稳态的生理作用。对给定apoLP的生理作用的理解取决于对蛋白质分子在可溶性和脂质结合状态下的结构和特性的了解。该项目的长期目标是在脂质结合状态下的载脂蛋白功能域的借出和表征。该建议涉及对两种载脂蛋白的结构和功能之间关系的研究：昆虫，载脂蛋白 - ill和人载脂蛋白A-I。该提案的具体目的包括：1）研究盘状HDL二倍蛋白中ApoA-I分子的组织； 2）对高密度脂蛋白中与脂质相​​互作用的人apoa-I区域的研究； 3）研究HDL颗粒中ApoA-I结构与脂蛋白功能之间的相关性。 4）研究载脂蛋白-III与磷脂单层和双层（包括天然脂蛋白和重建模型脂蛋白）的缔合机理；这些目标的实现对于充分理解涉及载脂蛋白的代谢途径的生理和病理是必要的。这包括了解载脂蛋白在脂质和相关病理的代谢中的作用，例如动脉粥样硬化，但它也可能涉及其他类型的病理，例如阿尔茨海默氏病。