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 binding, but it undergoes a metal-dependent conformational change with a 100 million-fold selectivity for Lns and Y over Ca. Here we present the nuclear magnetic resonance solution structure of LanM complexed with Y. 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 Lns, and it suggests a role of unusual N -H···N hydrogen bonds, in which LanM's unique EF-hand proline residues are engaged, in selective Ln 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.