Marsico Visiting Scholar Lecture

September 19

4:00pm - 5:00pm

Selective Recognition of Lanthanides in Biology and Biotechnology

Joeph Cortruvo, PhD
Department of Chemistry
Penn State University

Olin Hall 205

Lecture abstract: Lanthanides (Lns) have been shown recently to be essential cofactors in certain enzymes in methylotrophic bacteria, such asMethylobacterium extorquens, which play a key role in the global carbon cycle. Here we present the discovery and characterization of lanmodulin (LanM), a protein that uses metal-binding motifs (EF-hands) typically associated with Ca(II) binding to recognize Ln(III)s with several million-fold selectivity over Ca(II). LanM undergoes a large conformational change from a largely disordered state to a compact, ordered state in response to picomolar Ln(III)s, whereas it only responds to Ca(II) at near-millimolar concentrations. Our biochemical studies suggest that unique proline residues in LanM’s EF hands play a role in decoupling the conformational change from Ca(II) binding and therefore ensuring metal selectivity in vivo. We also present the NMR solution structure of the yttrium(III)-bound form of this protein, revealing a novel fold for an EF-hand protein and insight into lanthanide coordination. Finally, we also describe a selective and robust protein-based fluorescent sensor for Lns, based on lanmodulin, and its application in M. extorquens to identify the first transporter system involved in Ln uptake. Further characterization of systems involved in Ln acquisition, trafficking, and utilization may help to guide development of new strategies to detect and sequester Lns for technological purposes.