Antimicrobial activity of apolipoprotein A-I

载脂蛋白a - i （apoA-I）在胆固醇的转运和代谢中起着核心作用，这一点已经得到了很好的证实。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。我们打算研究apoa - 1与细菌膜的结合。初步研究表明，apoA-I与外膜脂多糖和内膜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。我们的目的是了解apoa - 1抗菌特性的分子基础。apoa - 1与来自不同细菌来源的各种LPS（包括截断的LPS版本）和来自内膜的磷脂的结合将被详细研究。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抗菌性能，我们将使用丙烯醛引起的自然发生的改性。这种物质大量存在于香烟烟雾中，目标是血清蛋白中的赖氨酸残基。经丙烯醛修饰后，与脂多糖、带负电荷的磷脂结合，抑制细菌生长。拟议的研究旨在更好地了解apoA-I如何识别细菌膜表面，从而提供抗革兰氏阴性感染的保护。通过这项研究获得的知识有可能导致改进的方法来管理尚无有效治疗方法的细菌性败血症。

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.