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钠氢交换体1亚型(NHE1)的结构与功能

Structure and function of the NHE1 isoform of the Na+/H+ exchanger.

作者信息

Slepkov Emily, Fliegel Larry

机构信息

Department of Biochemistry, Faculty of Medicine, Canadian Institutes of Health Research, University of Alberta, Edmonton.

出版信息

Biochem Cell Biol. 2002;80(5):499-508. doi: 10.1139/o02-151.

DOI:10.1139/o02-151
PMID:12440691
Abstract

The Na+/H+ exchanger is a ubiquitous, integral membrane protein involved in pH regulation. It removes intracellular acid, exchanging a proton for an extracellular sodium ion. There are seven known isoforms of this protein that are the products of distinct genes. The first isoform discovered (NHE1) is ubiquitously distributed throughout the plasma membrane of virtually all tissues. It plays many different physiological roles in mammals, including important functions in regulation of intracellular pH, in heart disease, and in cytoskeletal organization. The first 500 amino acids of the protein are believed to consist of 12 transmembrane helices, a membrane-associated segment, and two reentrant loops. A C-terminal regulatory domain of approximately 315 amino acids regulates the protein and mediates cytoskeletal interactions. Studies are underway to determine the amino acid residues important in NHE1 function. At present, it is clear that transmembrane segment IV is important in NHE1 function and that transmembrane segments VII and IX are also involved in transport. Further experiments are required to elucidate the mechanism of transport and regulation of this multifunctional protein.

摘要

钠氢交换体是一种广泛存在的整合膜蛋白,参与pH调节。它通过将一个质子与一个细胞外钠离子进行交换来清除细胞内的酸性物质。该蛋白有七种已知的同工型,它们是不同基因的产物。最早发现的同工型(NHE1)广泛分布于几乎所有组织的质膜中。它在哺乳动物中发挥着许多不同的生理作用,包括在调节细胞内pH、心脏病以及细胞骨架组织方面的重要功能。该蛋白的前500个氨基酸被认为由12个跨膜螺旋、一个膜相关片段和两个折返环组成。一个约315个氨基酸的C末端调节结构域对该蛋白进行调节并介导细胞骨架相互作用。目前正在进行研究以确定对NHE1功能重要的氨基酸残基。目前,很明显跨膜片段IV对NHE1功能很重要,并且跨膜片段VII和IX也参与转运。需要进一步的实验来阐明这种多功能蛋白的转运和调节机制。

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