Antimicrobial activity of apolipoprotein A-I

载脂蛋白 A-I 的抗菌活性

基本信息

项目摘要

DESCRIPTION (provided by applicant: Antimicrobial activity of apolipoprotein A-I It has been well established that the human serum protein apolipoprotein A-I (apoA-I) plays a central role in the transport and metabolism of cholesterol. However, it has become increasingly clear that the protein plays an important role in innate immunity as well. We propose to investigate the binding of apoA-I to bacterial membranes. Initial studies have shown that apoA-I binds to lipopolysaccharides of the outer membrane and negatively charged phospholipids of the inner membrane. Lysine residues play a critical role in this binding interaction. We aim to understand the molecular basis for the antimicrobial properties of apoA-I. The binding of apoA-I to a variety of LPS from different bacterial sources including truncated LPS versions, and phospholipids from in inner membrane, will be investigated in detail. This will provide key insight into the binding mechanism. Since neutralization of lysine residues inhibits antimicrobial properties, we will use a naturally occurring modification caused by acrolein. This agent is abundantly present in cigarette smoke targeting lysine residues in serum proteins. Upon modification by acrolein, binding to lipopolysaccharides, negatively charged phospholipids, and the inhibition of bacterial growth will be determined. The proposed studies aims to better understand how apoA-I recognizes bacterial membrane surfaces thereby providing protection against gram-negative infection. The knowledge obtained by this study has the potential to result in improved ways to manage bacterial sepsis for which no effective treatment exists.
描述(由申请人提供:载脂蛋白A-I的抗微生物活性已经充分证实,人血清蛋白载脂蛋白A-I(apoA-I)在胆固醇的转运和代谢中起着中心作用。然而,越来越清楚的是,这种蛋白质在先天免疫中也起着重要作用。我们建议调查apoA-I细菌膜的结合。初步研究表明,apoA-I与外膜的脂多糖和内膜的带负电荷的磷脂结合。赖氨酸残基在这种结合相互作用中起关键作用。我们的目标是了解apoA-I抗菌特性的分子基础。将详细研究apoA-I与来自不同细菌来源的各种LPS(包括截短的LPS版本)和来自内膜的磷脂的结合。这将提供对绑定机制的关键洞察。由于赖氨酸残基的中和抑制了抗菌性能,我们将使用由丙烯醛引起的天然存在的修饰。这种药剂大量存在于香烟烟雾中,靶向血清蛋白中的赖氨酸残基。在丙烯醛修饰后,将测定与脂多糖、带负电荷的磷脂的结合以及对细菌生长的抑制。拟议的研究旨在更好地了解apoA-I如何识别细菌膜表面,从而提供对革兰氏阴性菌感染的保护。本研究所获得的知识有可能导致改进的方法来管理细菌性脓毒症,因为没有有效的治疗方法。

项目成果

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PAUL Michiel WEERS其他文献

PAUL Michiel WEERS的其他文献

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{{ truncateString('PAUL Michiel WEERS', 18)}}的其他基金

Molecular mechanism of apolipoprotein binding to lipopolysaccharides
载脂蛋白与脂多糖结合的分子机制
  • 批准号:
    7761161
  • 财政年份:
    2010
  • 资助金额:
    $ 10.99万
  • 项目类别:
Antimicrobial activity of apolipoprotein A-I
载脂蛋白 A-I 的抗菌活性
  • 批准号:
    9310258
  • 财政年份:
    2010
  • 资助金额:
    $ 10.99万
  • 项目类别:
Antimicrobial activity of apolipoprotein A-I
载脂蛋白 A-I 的抗菌活性
  • 批准号:
    8741852
  • 财政年份:
    2010
  • 资助金额:
    $ 10.99万
  • 项目类别:
Mechanism of initiation of lipid binding of apolipoprotein A-I
载脂蛋白 A-I 脂质结合的启动机制
  • 批准号:
    10189632
  • 财政年份:
    2010
  • 资助金额:
    $ 10.99万
  • 项目类别:
Molecular mechanism of apolipoprotein binding to lipopolysaccharides
载脂蛋白与脂多糖结合的分子机制
  • 批准号:
    8208976
  • 财政年份:
    2010
  • 资助金额:
    $ 10.99万
  • 项目类别:
Antimicrobial activity of apolipoprotein A-I
载脂蛋白 A-I 的抗菌活性
  • 批准号:
    9114129
  • 财政年份:
    2010
  • 资助金额:
    $ 10.99万
  • 项目类别:
Mechanism of initiation of lipid binding of apolipoprotein A-I
载脂蛋白 A-I 脂质结合的启动机制
  • 批准号:
    10436238
  • 财政年份:
    2010
  • 资助金额:
    $ 10.99万
  • 项目类别:
Molecular mechanism of apolipoprotein binding to lipopolysaccharides
载脂蛋白与脂多糖结合的分子机制
  • 批准号:
    8005568
  • 财政年份:
    2010
  • 资助金额:
    $ 10.99万
  • 项目类别:
Molecular mechanism of apolipoprotein binding to lipopolysaccharides
载脂蛋白与脂多糖结合的分子机制
  • 批准号:
    8399726
  • 财政年份:
    2010
  • 资助金额:
    $ 10.99万
  • 项目类别:
Lipid-induced conformational switch of apolipophorin III
脂质诱导的载脂蛋白 III 构象转换
  • 批准号:
    6806133
  • 财政年份:
    2004
  • 资助金额:
    $ 10.99万
  • 项目类别:

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