Department of Biochemistry, University of Zurich, Zurich, Switzerland.
1] Structural Biology Research Center, Vlaams Instituut voor Biotechnologie (VIB), Brussels, Belgium. [2] Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
Nat Struct Mol Biol. 2014 Nov;21(11):990-6. doi: 10.1038/nsmb.2904. Epub 2014 Oct 19.
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.
SLC11（NRAMP）家族的成员在细胞膜内运输铁和其他过渡金属离子。这些膜蛋白存在于所有生命领域，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 DMT（ScaDMT）的晶体结构，这是该家族的一个密切的原核同源物。ScaDMT 显示出一种熟悉的结构，在氨基酸渗透酶 LeuT 中也有发现。该蛋白采用面向内的构象，其底物结合位点位于转运体的中心。该位点由保守残基组成，可协调 Mn2+、Fe2+和 Cd2+，但不协调 Ca2+。相互作用残基的突变会影响 ScaDMT 和人 DMT1 中的离子结合和运输。因此，我们的研究揭示了 SLC11 家族中过渡金属离子选择性的保守机制。
