Crystal structure of a SLC11 (NRAMP) transporter reveals the basis for transition-metal ion transport
Crystal structure of a SLC11 (NRAMP) transporter reveals the basis for transition-metal ion transport
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DOI：
10.1038/nsmb.2904
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发表时间：
2014-11-01
影响因子：
16.8
通讯作者：
Dutzler, Raimund
中科院分区：
文献类型：
--
作者：
Ehrnstorfer, Ines A.;Geertsma, Eric R.;Dutzler, Raimund
SLC 11（NRAMP）家族成员跨细胞膜转运铁和其他过渡金属离子。这些膜蛋白存在于所有生命界中，具有高度的序列保守性。为了深入了解离子选择性的决定因素，我们已经确定了葡萄球菌头DMT（ScaDMT），一个密切的原核同源家族的晶体结构。ScaDMT显示了以前在氨基酸通透酶LeuT中鉴定的熟悉结构。该蛋白质采用向内的构象，底物结合位点位于转运蛋白的中心。该位点由保守残基组成，它们与Mn ~（2+）、Fe ~（2+）和Cd ~（2+）配位，但不与Ca ~（2+）配位。相互作用残基的突变影响ScaDMT和人DMT 1中的离子结合和转运。因此，我们的研究揭示了SLC 11家族中过渡金属离子选择性的保守机制。
Members of the SLC11 (NRAMP) family transport iron and other transition-metal ions across cellular membranes. These membrane proteins are present in all kingdoms of life with a high degree of sequence conservation. To gain insight into the determinants of ion selectivity, we have determined the crystal structure of Staphylococcus capitis DMT (ScaDMT), a close prokaryotic homolog of the family. ScaDMT shows a familiar architecture that was previously identified in the amino acid permease LeuT. The protein adopts an inward-facing conformation with a substrate-binding site located in the center of the transporter. This site is composed of conserved residues, which coordinate Mn2+, Fe2+ and Cd2+ but not Ca2+. Mutations of interacting residues affect ion binding and transport in both ScaDMT and human DMT1. Our study thus reveals a conserved mechanism for transition-metal ion selectivity within the SLC11 family.