Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, U.S.A.
Biochem Soc Trans. 2023 Jun 28;51(3):897-923. doi: 10.1042/BST20210699.
A repertoire of transporters plays a crucial role in maintaining homeostasis of biologically essential transition metals, manganese, and iron, thus ensuring cell viability. Elucidating the structure and function of many of these transporters has provided substantial understanding into how these proteins help maintain the optimal cellular concentrations of these metals. In particular, recent high-resolution structures of several transporters bound to different metals enable an examination of how the coordination chemistry of metal ion-protein complexes can help us understand metal selectivity and specificity. In this review, we first provide a comprehensive list of both specific and broad-based transporters that contribute to cellular homeostasis of manganese (Mn2+) and iron (Fe2+ and Fe3+) in bacteria, plants, fungi, and animals. Furthermore, we explore the metal-binding sites of the available high-resolution metal-bound transporter structures (Nramps, ABC transporters, P-type ATPase) and provide a detailed analysis of their coordination spheres (ligands, bond lengths, bond angles, and overall geometry and coordination number). Combining this information with the measured binding affinity of the transporters towards different metals sheds light into the molecular basis of substrate selectivity and transport. Moreover, comparison of the transporters with some metal scavenging and storage proteins, which bind metal with high affinity, reveal how the coordination geometry and affinity trends reflect the biological role of individual proteins involved in the homeostasis of these essential transition metals.
转运蛋白在维持生物必需过渡金属锰和铁的体内平衡方面发挥着至关重要的作用，从而确保细胞的存活。阐明许多这些转运蛋白的结构和功能，为我们理解这些蛋白质如何帮助维持这些金属在细胞中的最佳浓度提供了重要的认识。特别是，最近几种转运蛋白与不同金属结合的高分辨率结构，使我们能够研究金属离子-蛋白质配合物的配位化学如何帮助我们理解金属的选择性和特异性。在这篇综述中，我们首先提供了一个全面的列表，列出了细菌、植物、真菌和动物中对锰（Mn2+）和铁（Fe2+和 Fe3+）细胞内平衡有贡献的特定和广泛的转运蛋白。此外，我们还研究了可用的高分辨率金属结合转运蛋白结构（Nramps、ABC 转运蛋白、P 型 ATP 酶）的金属结合位点，并对其配位球（配体、键长、键角、整体几何形状和配位数）进行了详细分析。将这些信息与转运蛋白对不同金属的结合亲和力的测量结果相结合，揭示了底物选择性和转运的分子基础。此外，将转运蛋白与一些具有高亲和力结合金属的金属清除和储存蛋白进行比较，揭示了配位几何形状和亲和力趋势如何反映参与这些必需过渡金属体内平衡的各个蛋白质的生物学作用。
