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STRUCTURE AND FUNCTION OF THE HIGH AFFINITY IGE RECEPTOR

高亲和力 IGE 受体的结构和功能

基本信息

批准号：
2886907
负责人：
MICHAEL W ROBERTSON
金额：
$ 12.25万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-08-01 至 2001-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2886907
关键词：
antibody receptor chimeric proteins immunoglobulin E molecular cloning nuclear magnetic resonance spectroscopy point mutation protein engineering protein structure function receptor binding

项目摘要

The high-affinity receptor (Fc epsilon RI) specific for immunoglobulin E (IgE) is found primarily on mast cells and basophils. Activation of these cells occurs in response to crosslinking of Fc epsilon RI with IgE-antigen complexes which initiates a cascade of cellular events culminating in the release of pharmacologically active substances that contribute to the clinical symptoms of many atopic disorders such as allergy, allergic asthma and immediate hypersensitivity. In this research program the structural features of Fc epsilon RI that contribute to specific receptor function will be explored. One goal is to define the molecular features of the Fc epsilon RI alpha-subunit involved in IgE binding. This will be approached using the dual approach of (i) protein engineering studies using both domain and point mutagenesis procedures and (ii) structure elucidation studies to be conducted initially using nuclear magnetic resonance spectroscopy in a collaborative study with Dr. A. Bax, National Institutes of Health. A parallel, but longer-term goal, is to generate receptor fragment crystals suitable for eventual crystallographic studies. Protein engineering studies will extensively utilize the powerful technique of phage display together with bacterial expression of Fc epsilon RI alpha fragments with subsequent physical characterization of ligand-binding activity. A long-term goal of this study is the precise definition of the 3-dimensional configuration of a "minimum complex" of Fc epsilon RI alpha-IgE. An additional but lower priority aim of this Proposal is to characterize the rat alpha-subunit ectodomain through detailed protein engineering studies, with the eventual goal of elucidating the 3-dimensional structure of this IgE-binding molecule. The requirement for Fc epsilon RI beta and/or gamma-subunit coexpression for rat-human alpha-chain ectodomain chimera will be explored as a means of probing the presumptive extracellular interaction of the receptor subunits. Progress in all of these studies should assist in the rational design of potential therapeutics for the treatment of atopic disorders. In addition, results should facilitate molecular studies of other immunologically important receptors [such as Fc gamma R] which are expected to share significant structural features with the IgE mast cell receptor.

免疫球蛋白E特异性高亲和受体（Fc epsilon RI）