A tale of two dimers: lanthanide recognition at biomolecular interfaces

Owing to minuscule differences in ionic radius and coordination numbers, separation of the lanthanides is technologically critical but rife with chemical and geopolitical challenges. Methylotrophic bacteria have evolved pathways for lanthanide acquisition and intracellular sorting of preferred from non-preferred lanthanides. Characterization of two proteins in this pathway, lanmodulin and landiscernin, has revealed mechanisms by which cells differentiate lanthanides. This review focuses on two modes of protein dimerization mediated by lanthanide ion binding at protein interfaces, which propagate picometer-scale differences in ionic radius to quaternary structure. Characterization of these interfaces has led us to propose a lanthanide trafficking pathway that ensures metalation of lanthanide-dependent enzymes. Finally, we discuss how metal ion-mediated protein dimerization may be applied toward improving industrial-scale lanthanide separations.