Dibrov P, Fliegel L
Department of Biochemistry, University of Alberta, Edmonton, Canada.
FEBS Lett. 1998 Mar 6;424(1-2):1-5. doi: 10.1016/s0014-5793(98)00119-7.
Despite 30 years of study on Na+/H+ exchange, the molecular mechanisms of antiport remain obscure. Most challenging, the identity of amino acids involved in binding transported cations is still unknown. We review data examining the identity of residues that are involved in cation binding and translocation of prokaryotic and eukaryotic Na+/H+ antiporters. Several polar residues specifically distributed within or immediately adjacent to membrane spanning regions are implicated as being important. These key amino acids are conserved in prokaryotes and in some lower eukaryotic forms of the Na+/ H+ antiporter, despite their being dispersed throughout the protein and despite an overall low similarity in the linear sequence of these Na+/H+ antiporters. We suggest that this conservation of isolated residues (together with distances between them) reflects a general physicochemical mechanism of cation binding by exchangers. The binding could be based on coordination of the substrate cation by a crown ether-like cluster of polar atomic groups amino acids, as has been hypothesized by Boyer. Traditional screening for the extended, highly conserved linear protein sequences might not be applicable when searching for functional domains of ion transporters. Three-dimensional constellations of polar residues (3D-motifs) may be evolutionary conserved rather than linear primary sequence.
尽管对Na+/H+交换进行了30年的研究，但反向转运的分子机制仍然不清楚。最具挑战性的是，参与结合转运阳离子的氨基酸身份仍然未知。我们回顾了有关原核生物和真核生物Na+/H+反向转运蛋白中参与阳离子结合和转运的残基身份的数据。几个特定分布在跨膜区域内或紧邻跨膜区域的极性残基被认为很重要。尽管这些关键氨基酸分散在整个蛋白质中，并且这些Na+/H+反向转运蛋白的线性序列总体相似性较低，但它们在原核生物和某些较低等真核生物形式的Na+/H+反向转运蛋白中是保守的。我们认为，这些孤立残基的保守性（以及它们之间的距离）反映了交换体结合阳离子的一般物理化学机制。正如博耶所假设的那样，这种结合可能基于极性原子基团氨基酸的冠醚样簇对底物阳离子的配位。在寻找离子转运蛋白的功能域时，传统的对延伸的、高度保守的线性蛋白质序列的筛选可能不适用。极性残基的三维组合（三维基序）可能在进化上是保守的，而不是线性一级序列。
