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RED CELL AQUAPORIN-1 WATER TRANSPORT PROTEIN

红细胞水通道蛋白-1 水运输蛋白

基本信息

批准号：
6536859
负责人：
Peter C Agre
金额：
$ 34.79万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-04-01 至 2005-03-31
项目状态：
已结题

项目摘要

DESCRIPTION: The human red cell membrane is the model upon which our general understanding of plasma membranes is based. Several membrane transport proteins have first been identified in red cells, and during previous years of this project, a 28kDa protein was discovered, purified, cloned, expressed and functionally defined in Dr. Agre's laboratory. Now designated AQP1, this protein is the first recognized membrane water transport molecule. While multiple homologous aquaporins are now becoming recognized in other tissues, physical studies of human red cell AQP1 are revealing its structure at subnanometer resolution and are providing advanced insight into the biophysical transport function of the molecule. Here Dr. Agre proposes studies to establish the molecular structure of AQP1 at near-atomic resolution and to define the behavior of AQP1 in membranes. Aim I. Structure and function of purified AQP1 protein. High resolution cryoelectron microscopic analysis of membrane crystals containing red cell AQP1 will be undertaken to elucidate the 3D structure of AQP1 at better than 3 resolution. Yeast and other heterologous systems will be developed to express mutagenized AQP1 molecules with specific epitopes for affinity-purifications, metal binding, definition of the aqueous pore, identification of the sites of ion repulsion and assembly of individual subunits into tetramers. Functional analysis of mutagenized forms of AQP1 will be determined by direct measurement of the water permeability of AQP1 proteins in yeast microsomal vesicles and in reconstituted proteoliposomes. Aim II. AQP1 protein in cell membranes. The Colton blood group antigens result from a polymorphism in the first extracellular loop of the AQP1 protein. Using fluorescently labeled-anti-Co, Dr. Agre plans to characterize the surface equilibrium distributions of AQP1 on normal red cells by immunofluorescence, immunoprecipitations, and flow sorting. Kinetic distributions of AQP1 in red cell membranes will be undertaken with anti-Co by measurement of fluorescence recovery after photobleaching. Similar studies will be performed on enzymatically modified red cells and red cells from patients with sickle cell anemia and other congenital hemolytic states. These abnormal red cells and AQP1 deficient red cells will also be examined for membrane water permeabilities. To fully define the molecular determinants of the Co antigen, nonerythroid cells will be studied for Co expression by transfection with mutagenized forms of AQP1.

人体红细胞膜是我们的

项目成果

期刊论文数量（46）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Purification and partial characterization of the Mr 30,000 integral membrane protein associated with the erythrocyte Rh(D) antigen.

与红细胞 Rh(D) 抗原相关的 Mr 30,000 整合膜蛋白的纯化和部分表征。

DOI：
发表时间：
1987
期刊：
The Journal of biological chemistry
影响因子：
0
作者：
Agre,P;Saboori,AM;Asimos,A;Smith,BL
通讯作者：
Smith,BL

Surface topographies at subnanometer-resolution reveal asymmetry and sidedness of aquaporin-1.

亚纳米分辨率的表面形貌揭示了 aquaporin-1 的不对称性和侧面性。

DOI：
10.1006/jmbi.1996.0686
发表时间：
1996
期刊：
Journal of molecular biology.
影响因子：
0
作者：
Walz,T;Tittmann,P;Fuchs,KH;Muller,DJ;Smith,BL;Agre,P;Gross,H;Engel,A
通讯作者：
Engel,A

Polymorphism in the Mr 32,000 Rh protein purified from Rh(D)-positive and -negative erythrocytes.

从 Rh(D) 阳性和阴性红细胞中纯化的 Mr 32,000 Rh 蛋白的多态性。

DOI：
10.1073/pnas.85.11.4042
发表时间：
1988
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Saboori,AM;Smith,BL;Agre,P
通讯作者：
Agre,P

Expression of the Rh-related glycoprotein (Rh50).

Rh 相关糖蛋白 (Rh50) 的表达。