Cation diffusion facilitator (CDF) proteins are a conserved family of divalent transition metal cation transporters. CDF proteins are usually composed of two domains: the transmembrane domain, in which the metal cations are transported through, and a regulatory cytoplasmic C-terminal domain (CTD). Each CDF protein transports either one specific metal or multiple metals from the cytoplasm, and it is not known whether the CTD takes an active regulatory role in metal recognition and discrimination during cation transport. Here, the model CDF protein MamM, an iron transporter from magnetotactic bacteria, was used to probe the role of the CTD in metal recognition and selectivity. Using a combination of biophysical and structural approaches, the binding of different metals to MamM CTD was characterized. Results reveal that different metals bind distinctively to MamM CTD in terms of their binding sites, thermodynamics, and binding-dependent conformations, both in crystal form and in solution, which suggests a varying level of functional discrimination between CDF domains. Furthermore, these results provide the first direct evidence that CDF CTDs play a role in metal selectivity. We demonstrate that MamM's CTD can discriminate against Mn2+, supporting its postulated role in preventing magnetite formation poisoning in magnetotactic bacteria via Mn2+ incorporation.

中文翻译：

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阳离子扩散促进蛋白MamM的胞质域表现出金属类型依赖性的结合模式，并区别于Mn2。

阳离子扩散促进剂（CDF）蛋白是二价过渡金属阳离子转运蛋白的保守家族。CDF蛋白通常由两个结构域组成：跨膜结构域（TMD）（其中的金属阳离子通过该结构域运输）和调节性细胞质C末端结构域（CTD）。每种CDF蛋白都从细胞质中转运出一种或多种特定金属，目前尚不知道CTD在阳离子转运过程中是否对金属的识别和识别起着积极的调节作用。在这里，模型CDF蛋白MamM是一种来自趋磁细菌的铁转运蛋白，用于探测CTD在金属识别和选择性中的作用。结合生物物理和结构方法，表征了不同金属与MamM CTD的结合。结果表明，不同的金属在晶体形式和溶液形式方面均在结合位点，热力学和结合依赖性构象方面与MamM CTD显着结合，这表明CDF域之间的功能区分水平不同。此外，这些结果提供了CDF CTD在金属选择性中起作用的第一个直接证据。我们证明，MamM的CTD可以区分Mn2 +，支持其假定的作用，以防止通过Mn2 +掺入在趋磁细菌中形成磁铁矿中毒。这些结果提供了直接的直接证据，证明CDF CTD在金属选择性中起作用。我们证明，MamM的CTD可以区分Mn2 +，支持其假定的作用，以防止通过Mn2 +掺入在趋磁细菌中形成磁铁矿中毒。这些结果提供了直接的直接证据，证明CDF CTD在金属选择性中起作用。我们证明，MamM的CTD可以区分Mn2 +，支持其假定的作用，以防止通过Mn2 +掺入在趋磁细菌中形成磁铁矿中毒。