Department of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute and Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
Department of Biophysics, Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, Bd. Eroii Sanitari 8, 050474 Bucharest, Romania.
Int J Mol Sci. 2022 Aug 15;23(16):9156. doi: 10.3390/ijms23169156.
Na/H exchangers are essential for Na and pH homeostasis in all organisms. Human Na/H exchangers are of high medical interest, and insights into their structure and function are aided by the investigation of prokaryotic homologues. Most prokaryotic Na/H exchangers belong to either the Cation/Proton Antiporter (CPA) superfamily, the Ion Transport (IT) superfamily, or the Na-translocating Mrp transporter superfamily. Several structures have been solved so far for CPA and Mrp members, but none for the IT members. NhaA from has served as the prototype of Na/H exchangers due to the high amount of structural and functional data available. Recent structures from other CPA exchangers, together with diverse functional information, have allowed elucidation of some common working principles shared by Na/H exchangers from different families, such as the type of residues involved in the substrate binding and even a simple mechanism sufficient to explain the pH regulation in the CPA and IT superfamilies. Here, we review several aspects of prokaryotic Na/H exchanger structure and function, discussing the similarities and differences between different transporters, with a focus on the CPA and IT exchangers. We also discuss the proposed transport mechanisms for Na/H exchangers that explain their highly pH-regulated activity profile.
Na/H 交换器对于所有生物体的 Na 和 pH 平衡至关重要。人类 Na/H 交换器具有很高的医学意义，通过研究原核同源物，可以深入了解其结构和功能。大多数原核 Na/H 交换器属于阳离子/质子反向转运体（CPA）超家族、离子转运（IT）超家族或 Na 转运 Mrp 转运体超家族。迄今为止，已经解决了一些 CPA 和 Mrp 成员的结构，但没有解决 IT 成员的结构。由于可获得大量结构和功能数据，因此来自 的 NhaA 一直被用作 Na/H 交换器的原型。来自其他 CPA 交换器的最新结构以及各种功能信息，阐明了不同家族的 Na/H 交换器之间共享的一些共同工作原理，例如参与底物结合的残基类型，甚至是一个简单的机制足以解释 CPA 和 IT 超家族中的 pH 调节。在这里，我们回顾了原核 Na/H 交换器结构和功能的几个方面，讨论了不同转运蛋白之间的相似点和不同点，重点是 CPA 和 IT 交换器。我们还讨论了 Na/H 交换器的拟议转运机制，该机制解释了其高度 pH 调节的活性特征。
