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Structural Thermodynamics of Human Apolipoprotein C-1

Structural Thermodynamics of Human Apolipoprotein C-1
人载脂蛋白 C-1 的结构热力学
批准号:
6982819
负责人:
Olga Gursky
金额:
$28.07万
依托单位国家:
美国
项目类别:
财政年份:
1998
资助国家:
美国
项目状态:
已结题
起止时间:
1998-12-15 至 2008-05-31

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中文摘要
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英文摘要
EXCEED THE SPACE PROVIDED. The long-term objective of this project is to determine in molecular detail the energetic-structure-function relationship in exchangeable apolipoproteins and lipoproteins, thereby providing an insight into molecular mechanisms of lipoprotein action in the pathogenesis of atherosclerosis and other Upoprotein-related diseases. Exchangeable apolipoproteins are soluble protein components of lipoproteins that mediate lipid and cholesterol transport and metabolism and play crucial roles in the pathogenesis of atherosclerosis, coronary heart disease, stroke and other major human disorders. Structural stability and compositional variability of lipoproteins are essential for their functions, and have to be understood in detail in order to elucidate molecular mechanisms of lipoprotein action in normal and in diseased states. The proposed work addresses this long-term goal through detailed studies of the energetics, structure and lipid binding function of two small human plasma apolipoproteins, apoC-1 and apoA-2. ApoC-1 delays the clearance of potentially atherogenic triglyceride-rich particles by inhibiting their uptake via the apoE-mediated low-density lipoprotein receptor-related pathway. The ability of apoC-1 to activate lecitin:cholesterol acyltransferase (LCAT) may account for normal plasma levels of cholesterol esters in subjects with deficiency of the major LCAT activator, apoA-1. ApoA-2 ability to displace apoA-1 from high-density lipoproteins (HDL) affects the antiatherogenic functions of HDL. Energetic and structural analyses of lipid-free and lipid-bound human apoA-2, apoC-1 and a series of apoC-1 mutants targeted towards key structural regions will be carried out by using a combination of far- and near-UV circular dichroism and fluorescence spectroscopy, electron microscopy, differential scanning calorimetry, and x-ray diffraction methods. Such analysis will determine, at the level of individual amino acids, the roles of key structural elements in apoC-1 for its folding, stability and lipid binding properties; identify critical determinants for the Lp stability and their relation to the kinetics of apolipoprotein transfer among lipoproteins in the course of lipoprotein metabolism; crystallize apoC-1 and analyze its crystal structure that may provide a model for a functional apolipoprotein conformation. The results will provide the energetic and structural basis for understanding molecular mechanisms of lipoprotein action in normal and diseased states.
期刊论文(5)
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会议论文
Probing the conformation of a human apolipoprotein C-1 by amino acid substitutions and trimethylamine-N-oxide.
通过氨基酸取代和三甲胺-N-氧化物探测人载脂蛋白 C-1 的构象。
DOI: 10.1110/ps.8.10.2055
发表时间: 1999
期刊: Protein science : a publication of the Protein Society
影响因子: --
作者: [Gursky,O]
通讯作者: Gursky,O
DOI: 10.1021/bi025588w
发表时间: 2002-06-11
期刊: BIOCHEMISTRY
影响因子: 2.9
作者: [Gursky, O, Ranjana, Gantz, DL]
通讯作者: Gantz, DL
Structure and Function of Serum Amyloid A in Health and Disease
  • 批准号:
    10543430
  • 项目类别:
  • 资助金额:
    $31.35万
  • 财政年份:
    2020
  • 负责人:
    Olga Gursky
  • 依托单位:
Structure and Function of Serum Amyloid A in Health and Disease
  • 批准号:
    10321653
  • 项目类别:
  • 资助金额:
    $31.35万
  • 财政年份:
    2020
  • 负责人:
    Olga Gursky
  • 依托单位:
Structure and Function of Serum Amyloid A in Health and Disease
  • 批准号:
    10580338
  • 项目类别:
  • 资助金额:
    $15.86万
  • 财政年份:
    2020
  • 负责人:
    Olga Gursky
  • 依托单位:
Structure and Function of Serum Amyloid A in Health and Disease
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