Coordination to lanthanide ions distorts binding site conformation in calmodulin

Calmodulin is essential to life in all eukaryotic cells and serves as a popular model for ion binding and activation in proteins. Calmodulin transduces complex calcium signals and acts on hundreds of effector proteins, but the sensitivity and complexity of this process make it difficult to characterize. Much work uses lanthanides as luminescent calcium substitutes to study ion binding and activation in calmodulin and other proteins. Using ultrafast 2D IR spectroscopy, we show that lanthanide ions perturb the finely tuned structure and dynamics of calmodulin's binding sites. The temporal and spatial resolution of our measurements opens a new window into the study of protein-ion binding and demonstrates that seemingly innocuous ligand substitutions can significantly alter protein conformation.