MECHANISM OF HEME CAPTURE BY THE HEMOPHORE SECRETED BY PSEUDOMONAS AERUGINOSA

铜绿假单胞菌分泌的血红素捕获血红素的机制

基本信息

批准号：
7959522
负责人：
Mario Rivera
金额：
$ 2.91万
依托单位：
UNIVERSITY OF KANSAS LAWRENCE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-01 至 2010-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7959522
关键词：
Binding Complex Computer Retrieval of Information on Scientific Projects Database Extracellular Space Funding Goals Grant Heme Hemoglobin Human Indium Institution Iron Mammals Membrane Molecular Play Proteins Pseudomonas aeruginosa Research Research Personnel Resources Role Source System Theft United States National Institutes of Health heme a insight molecular recognition pathogenic bacteria protein protein interaction protein structure function receptor three dimensional structure

Binding Complex Computer Retrieval of Information on Scientific Projects Database Extracellular Space Funding Goals Grant Heme Hemoglobin Human Indium Institution Iron Mammals Membrane Molecular Play Proteins Pseudomonas aeruginosa Research Research Personnel Resources Role Source System Theft United States National Institutes of Health heme a insight molecular recognition pathogenic bacteria protein protein interaction protein structure function receptor three dimensional structure

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项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Heme is the most abundant source of circulating iron in mammals. It is therefore not surprising that many pathogenic bacteria, including the opportunistic Pseudomonas aeruginosa, avidly pursue its capture and internalization to overcome the very low free-iron concentrations encountered in their mammalian hosts. To capture heme, several pathogenic bacteria, including P. aeruginosa, deploy a heme acquisition system (Has), which consists of a protein secreted to the extracellular space (HasAp) and an outer membrane receptor (HasR). HasAp is also termed a hemophore because it efficiently captures hemoglobin-heme and delivers it to the receptor for subsequent internalization. The studies proposed herein aim to achieve fundamental molecular level understanding of the protein-protein interactions that allow HasAp to "steal" heme from human hemoglobin. In particular, the investigators seek to gain unprecedented structural, dynamic and mechanistic insights into the factors that determine the transfer of heme from human hemoglobin to HasAp. This long-range goal will be reached by pursuing two main objectives: 1) Elucidate the three dimensional structure of apo-HasAp, 2) Identify the binding interface of the encounter complex that forms when HasAp binds to hemoglobin, prior to heme transfer, and decipher the role played by the gross reorganization of HasAp structural elements in the molecular recognition and binding to hemoglobin.

该副本是利用众多研究子项目之一由NIH/NCRR资助的中心赠款提供的资源。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构是对于中心，这不一定是调查员的机构。血红素是哺乳动物中循环铁的最丰富来源。因此，毫不奇怪，许多病原细菌（包括机会性铜绿假单胞菌）狂热地追求其捕获和内在化，以克服其哺乳动物宿主中遇到的非常低的自由铁浓度。为了捕获血红素，包括铜绿假单胞菌在内的几种致病细菌部署血红素采集系统（HAS），该系统由分泌到细胞外空间（Hasap）和外膜受体（Hasr）的蛋白质组成。 HASAP也被称为嗜血杆菌，因为它有效地捕获了血红蛋白 - 血红素并将其传递给受体以进行后续内在化。本文提出的研究旨在实现对蛋白质蛋白质相互作用的基本分子水平的理解，这些相互作用允许哈比从人血红蛋白中“窃取”血红素。特别是，研究人员寻求对确定血红素从人血红蛋白转移到哈希的转移的因素来获得前所未有的结构，动态和机械见解。 This long-range goal will be reached by pursuing two main objectives: 1) Elucidate the three dimensional structure of apo-HasAp, 2) Identify the binding interface of the encounter complex that forms when HasAp binds to hemoglobin, prior to heme transfer, and decipher the role played by the gross reorganization of HasAp structural elements in the molecular recognition and binding to hemoglobin.