Abstract

Lanthanides (Lns) have been shown recently to be essential cofactors in certain enzymes in methylotrophic bacteria. Here we identify in the model methylotroph, Methylobacterium extorquens, a highly selective LnIII-binding protein, which we name lanmodulin (LanM). LanM possesses four metal-binding EF hand motifs, commonly associated with CaII-binding proteins. In contrast to other EF hand containing proteins, however, LanM undergoes a large conformational change from a largely disordered state to a compact, ordered state in response to picomolar concentrations of all LnIII (Ln = La−Lu, Y), whereas it only responds to CaII at near millimolar concentrations. Mutagenesis of conserved proline residues present in LanM’s EF hands, not encountered in CaII-binding EF hands, to alanine pushes CaII responsiveness into the micromolar concentration range while retaining picomolar LnIII affinity, suggesting that these unique proline residues play a key role in ensuring metal selectivity in vivo. Identification and characterization of LanM provides insights into how biology selectively recognizes low-abundance LnIII over higher-abundance CaII, pointing toward biotechnologies for detecting, sequestering, and separating these technologically important elements.

Submission Details

ID: SBdgdsUS3

Submitter: Carlo Martin Ocampo

Submission Date: June 5, 2023, 3:35 a.m.

Version: 1

Publication Details

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