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STRUCTURE AND FUNCTION OF GP-330

GP-330的结构和功能

基本信息

批准号：
2016646
负责人：
ROBERT T MCCLUSKEY
金额：
$ 23.72万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
1993
资助国家：
美国
起止时间：
1993-12-15 至 1998-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2016646
关键词：
antigen receptors autoantibody complementary DNA epithelium glycoprotein structure glycoproteins immune complex diseases laboratory rat low density lipoprotein receptor membranous glomerulonephritis monoclonal antibody nucleic acid sequence polymerase chain reaction protein structure function receptor mediated endocytosis southern blotting transfection

项目摘要

The main goal of this project is to investigate the structure, function and pathogenic role of a large glycoprotein called gp 330. This molecule was first identified as a major pathogenic antigen in Heymann nephritis - a rat model of human membranous glomerulonephritis. In a later study, the primary structure of gp 330, as deduced from partial cDNAs, was found to have considerable homology to the low density lipoprotein (LDL) receptor and the LDL receptor related protein (LRP), also known as the alpha2 macroglobulin receptor (alpha2MR). Recently, it has been shown that several known ligands of LRP/alpha2 MR bind to gp 330 in vitro, but the physiologic relevance of these observations is unknown, since gp 330 and LRP/alpha2MR have quite different distributions in vivo. Gp 330 is largely restricted to a group of epithelial cells whose major function appears to be absorption. A 39-44 KD protein invariably co-purifies with gp 330 and LRP/alpha2MR; this receptor associated protein (alpha2MRAP) inhibits the binding of ligands to gp 330 or LRP/alpha2MR in vitro, but its role in vivo is unknown. Major goals of this project are to obtain a full length cDNA encoding gp 330, investigate its receptor function in vivo, and to clarify the function of alpha2MRAP. In addition, the role of alpha2MRAP, gp 330 and ligands of gp 330 in the development of immune deposits in Heymann nephritis will be studied. The research may provide information about the receptor function of gp 330 and its role in specialized epithelial cells. The studies on Heymann nephritis should reveal new information about how immune deposits form in glomeruli, which is an important mechanism in major forms of human glomerulonephritis.

本项目的主要目标是研究其结构、功能以及称为GP 330的大糖蛋白的致病作用。这种分子首次被鉴定为Heymann肾炎的主要致病抗原- 人膜性肾小球肾炎的大鼠模型。在后来的一项研究中，从部分cDNA推导出的gp 330的一级结构，与低密度脂蛋白（LDL）受体具有相当大的同源性和LDL受体相关蛋白（LRP），也称为α 2 巨球蛋白受体（α 2 MR）。最近的研究表明，几种已知的LRP/α 2 MR配体在体外与gp 330结合，但这些观察结果的生理相关性尚不清楚，因为gp 330和 LRP/α 2 MR在体内的分布差异很大。第330章很大程度上仅限于一组上皮细胞，其主要功能似乎吸收。39-44 KD蛋白总是与gp 330共纯化， LRP/α 2 MR;这种受体相关蛋白（α 2 MRAP）抑制体外配体与gp 330或LRP/α 2 MR的结合，但其在 vivo未知本项目的主要目标是获得编码gp的全长cDNA， 330，研究其在体内的受体功能，并阐明其在体内的作用。 alpha 2 MRAP的功能此外，α 2 MRAP、gp 330和 GP 330配体在Heymann免疫沉积物形成中的作用将研究肾炎。这项研究可以提供有关 gp 330的受体功能及其在特化上皮细胞中的作用海曼肾炎的研究应该揭示新的信息，免疫沉积物在肾小球中形成，这是人类肾小球肾炎的主要形式。