Antimicrobial activity of apolipoprotein A-I

载脂蛋白 A-I 的抗菌活性

基本信息

批准号：
8911329
负责人：
PAUL Michiel WEERS
金额：
$ 10.99万
依托单位：
CALIFORNIA STATE UNIVERSITY LONG BEACH
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-01-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8911329
关键词：
Acetylation Acrolein Address Affect Aldehydes Alkaline Phosphatase Anti-Bacterial Agents Antiatherogenic Apolipoprotein A-I Apolipoproteins Apoptosis Bacteria Bacterial Infections Binding Biological Assay Carbohydrates Cardiovascular Diseases Cell membrane Charge Cholesterol Homeostasis Disease Endotoxins Gram-Negative Bacteria Growth Health High Density Lipoproteins Human Infection Inflammation Knowledge Lead Life Lipid A Lipid Binding Lipids Lipopolysaccharides Lipoproteins Lysine Mediating Membrane Modification Molecular Muramidase Natural Immunity Phosphatidylglycerols Phospholipids Play Prevention Property Proteins Role Sepsis Serotyping Serum Serum Proteins Side Source Structure Surface antimicrobial base cigarette smoking effective therapy flexibility improved in vivo inorganic phosphate insight interest lipid transport mortality novel protein folding protein function reconstitution reverse cholesterol transport

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.