Department of Chemistry, The Pennsylvania State University, University Park, PA 16802.
Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802.
Proc Natl Acad Sci U S A. 2024 Nov 5;121(45):e2410926121. doi: 10.1073/pnas.2410926121. Epub 2024 Oct 28.
Elucidating details of biology's selective uptake and trafficking of rare earth elements, particularly the lanthanides, has the potential to inspire sustainable biomolecular separations of these essential metals for myriad modern technologies. Here, we biochemically and structurally characterize () LanD, a periplasmic protein from a bacterial gene cluster for lanthanide uptake. This protein provides only four ligands at its surface-exposed lanthanide-binding site, allowing for metal-centered protein dimerization that favors the largest lanthanide, La. However, the monomer prefers Nd and Sm, which are disfavored lanthanides for cellular utilization. Structure-guided mutagenesis of a metal-ligand and an outer-sphere residue weakens metal binding to the LanD monomer and enhances dimerization for Pr and Nd by 100-fold. Selective dimerization enriches high-value Pr and Nd relative to low-value La and Ce in an all-aqueous process, achieving higher separation factors than lanmodulins and comparable or better separation factors than common industrial extractants. Finally, we show that LanD interacts with lanmodulin (LanM), a previously characterized periplasmic protein that shares LanD's preference for Nd and Sm. Our results suggest that LanD's unusual metal-binding site transfers less-desirable lanthanides to LanM to siphon them away from the pathway for cytosolic import. The properties of LanD show how relatively weak chelators can achieve high selectivity, and they form the basis for the design of protein dimers for separation of adjacent lanthanide pairs and other metal ions.
阐明生物对稀土元素（尤其是镧系元素）的选择性摄取和转运的细节，有可能启发人们对这些重要金属进行可持续的生物分子分离，以满足众多现代技术的需求。在这里，我们通过生物化学和结构分析对（）LanD 进行了表征，这是一种细菌基因簇中用于镧系元素摄取的周质蛋白。该蛋白在其表面暴露的镧系元素结合位点仅提供四个配体，允许金属中心的蛋白二聚化，从而有利于最大的镧系元素镧。然而，单体更倾向于钕和钐，它们是细胞利用中不利的镧系元素。对金属配体和外部球体残基的结构引导诱变削弱了 LanD 单体对金属的结合，并使 Pr 和 Nd 的二聚化增强了 100 倍。选择性二聚化使高价值的 Pr 和 Nd 相对于低价值的 La 和 Ce 在全水过程中得到富集，实现了比 lanmodulins 更高的分离因子，并且与常见的工业萃取剂相比，分离因子相当或更好。最后，我们表明 LanD 与先前表征的周质蛋白 LanM 相互作用，LanM 对 Nd 和 Sm 具有与 LanD 相同的偏好。我们的结果表明，LanD 不寻常的金属结合位点将不太理想的镧系元素转移到 LanM 上，从而将它们从细胞质内导入途径中吸走。LanD 的特性表明，相对较弱的螯合剂如何实现高选择性，并且它们为分离相邻镧系元素对和其他金属离子的蛋白二聚体的设计提供了基础。
