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Structure and function of proteins to form complex with receptor for heat-stable enterotoxin

与热稳定肠毒素受体形成复合物的蛋白质的结构和功能

基本信息

批准号：
06680583
负责人：
OZAKI Hiroshi
金额：
$ 0.38万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06680583/
关键词：
heat-stable enterotoxin ST-receptor Fluorophor porification membrane protein

项目摘要

Heat-stable enterotoxin (STs) produced by enterotoxigenic Escherichia coli are known to cause an acute diarrhea in men and animals. The biological action of ST is initiated by the binding to its receptor proteins on the membrane of intestinal epithelial cell. The formation of a ST-receptor complex leads to stimulation of guanylate cyclase and is followed by increase in cGMP concentration in the cells. Protein kinase is activated by the binding with cGMP and activate Cystic fibrosis transmembrane conductance regulator to result in a fluid secretion from the cells. In a course of study to purify receptor proteins for ST from rat intestine, receptor protein was found to form receptor protein complex. To elucidate the signal transduction mechanism by ST,it is important to know whether ST-receptor complex is the homo-oligomer or the hetero-oligomer with different proteins. Purpose of this study is to elucidate the structure and functions of proteins which forms complex with receptor protein for ST.To accomplish this purpose, ST analogs were designed to have the fluorophore, the functional group for the cross-linking to the receptor protein, and the specific binding ability to the receptor protein corresponding to that of the native ST and were synthesized. Binding characteristics of ST to the membrane prepared from rat intestine were investigated. Results revealed that membrane contained two types of receptor proteins, that is, one binds exchange-ably with ST (Rex) and the other non-echange-ably (Rnex). Rnex existed on membrane in two kinds of receptor complexes ((1) and (2)). (1) and (2) were found to be constructed with common protein components and the different component to each other. Among these proteins, analysis of common components are in progress.

产肠毒素大肠埃希菌产生的耐热肠毒素(STS)可引起人和动物的急性腹泻。ST的生物学作用是通过与肠上皮细胞膜上的ST受体蛋白结合而启动的。ST-受体复合体的形成导致鸟苷环化酶的刺激，随之而来的是细胞内cGMP浓度的增加。蛋白激酶通过与cGMP的结合而被激活，并激活囊性纤维化跨膜电导调节因子，导致细胞分泌液体。在从大鼠肠道中提纯ST受体蛋白的过程中，发现受体蛋白形成受体蛋白复合体。为了阐明ST的信号转导机制，重要的是要知道ST-受体复合体是同源低聚物还是含有不同蛋白质的异源低聚物。本研究的目的是阐明ST与受体蛋白形成复合物的蛋白质的结构和功能。为了实现这一目的，设计了ST类似物，使其具有与受体蛋白交联的荧光团和与受体蛋白的特异性结合能力，与天然ST的结合能力相当于天然ST。研究了ST与大鼠肠膜的结合特性。结果表明，膜上含有两种受体蛋白，一种与ST(Rex)可交换结合，另一种不可改变(RneX)。RneX存在于两种受体复合体(1)和(2)的膜上。(1)和(2)分别由相同的蛋白质组分和不同的蛋白质组分组成。在这些蛋白质中，对共同成分的分析正在进行中。