Structural Basis for Rare Earth Element Recognition by Methylobacterium extorquens Lanmodulin

Lanmodulin (LanM) is a high-affinity lanthanide (Ln)-binding protein recently identified in Methylobacterium extorquens, a bacterium that requires Lns for the function of at least two enzymes. LanM possesses four EF-hands, metal coordination motifs generally associated with Ca ^II binding, but it undergoes a metal-dependent conformational change with a 100 million-fold selectivity for Ln ^III s and Y ^III over Ca ^II . Here we present the nuclear magnetic resonance solution structure of LanM complexed with Y ^III . This structure reveals that LanM features an unusual fusion of adjacent EF-hands, resulting in a compact fold to the best of our knowledge unique among EF-hand-containing proteins. It also supports the importance of an additional carboxylate ligand in contributing to the protein's picomolar affinity for Ln ^III s, and it suggests a role of unusual N _i+1 -H···N _i hydrogen bonds, in which LanM's unique EF-hand proline residues are engaged, in selective Ln ^III recognition. This work sets the stage for a detailed mechanistic understanding of LanM's Ln selectivity, which may inspire new strategies for binding, detecting, and sequestering these technologically important metals.