Outward- and inward-facing structures of a putative bacterial transition-metal transporter with homology to ferroportin.
Outward- and inward-facing structures of a putative bacterial transition-metal transporter with homology to ferroportin.
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DOI：
10.1038/ncomms9545
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发表时间：
2015-10-13
影响因子：
16.6
通讯作者：
Nureki O
中科院分区：
文献类型：
--
作者：
Taniguchi R;Kato HE;Font J;Deshpande CN;Wada M;Ito K;Ishitani R;Jormakka M;Nureki O
在脊椎动物中，铁转运蛋白将Fe 2+从细胞释放到血浆中，从而维持铁稳态。膜铁转运蛋白的转运活性受到肽激素铁调素的抑制，其在慢性炎症中表现出上调的表达，引起铁限制性贫血。然而，由于缺乏关于ferroportin的结构信息，其铁转运和铁调素介导的调节机制仍然很难理解。在这里，我们报告的晶体结构的一个假定的细菌同源的ferroportin，BbFPN，在外向和内向的状态。尽管检测不到序列相似性，BbFPN采用主要的促进超家族折叠。这两种结构的比较表明，BbFPN在运输周期中经历了结构域内构象重排。我们确定了一个基板金属结合位点，基于结构和突变分析。此外，BbFPN结构表明，铁转运蛋白的预测hepcidin结合位点位于其中央腔。因此，BbFPN可能是一个有价值的结构模型，铁稳态调控的ferroportin。 脊椎动物细胞的铁输出由膜铁转运蛋白介导，膜铁转运蛋白被肽激素铁调素抑制。Taniguchi等人提出了一种假定的细菌ferroportin同系物在外向和内向状态下的晶体结构，提供了对其运输机制的深入了解。
In vertebrates, the iron exporter ferroportin releases Fe2+ from cells into plasma, thereby maintaining iron homeostasis. The transport activity of ferroportin is suppressed by the peptide hormone hepcidin, which exhibits upregulated expression in chronic inflammation, causing iron-restrictive anaemia. However, due to the lack of structural information about ferroportin, the mechanisms of its iron transport and hepcidin-mediated regulation remain largely elusive. Here we report the crystal structures of a putative bacterial homologue of ferroportin, BbFPN, in both the outward- and inward-facing states. Despite undetectable sequence similarity, BbFPN adopts the major facilitator superfamily fold. A comparison of the two structures reveals that BbFPN undergoes an intra-domain conformational rearrangement during the transport cycle. We identify a substrate metal-binding site, based on structural and mutational analyses. Furthermore, the BbFPN structures suggest that a predicted hepcidin-binding site of ferroportin is located within its central cavity. Thus, BbFPN may be a valuable structural model for iron homeostasis regulation by ferroportin. Iron export from vertebrate cells is mediated by ferroportin, which is suppressed by the peptide hormone hepcidin. Taniguchi et al. present crystal structures of a putative bacterial ferroportin homologue in both outward- and inward-facing states, providing insight into its transport mechanism.