J. Am. Chem. Soc. 140, 15056–15061 (2018)

Biochemistry https://doi.org/10.1021/acs.biochem.8b01019 (2018)

Certain methylotrophic bacteria use lanthanides as cofactors in methanol dehydrogenase and other metalloenzymes. While studying how these enzymes selectively incorporate lanthanides, Cotruvo et al. identified a new type of lanthanide-binding protein, lanmodulin (LanM), in Methylobacterium extorquens. LanM contains four carboxylate-rich EF hand motifs similar to those found in the eukaryotic calcium-binding protein calmodulin, but with additional aspartate and proline residues. An NMR solution structure of LanM bound to yttrium, determined by Cook et al., also revealed that adjacent EF hands are unusually fused. In vitro, metal-free LanM is relatively disordered, but lanthanide binding induces a conformational change to a more ordered state. By contrast, LanM’s response to calcium is much weaker, indicating ~108-fold selectivity. Mutation of the proline residues in the EF hands made LanM more sensitive to calcium, indicating the importance of these residues in selecting for lanthanides over a more abundant metal. Although the role of this protein in bacteria has yet to be determined, the characterization of LanM and its homologs may help to understand how methylotrophic bacteria process these uncommon metals.

figure a

ACS