Infrared probes of ion specificity in signaling metalloproteins and model ion-binding compounds

Ion-sensing proteins play critical and varied roles in hundreds of biological signaling pathways that are essential to human health and implicated in diseases ranging from cardiac arrhythmia to cancer. Central to the function of these biomolecules are compact ion recognition domains that drive global structural reconfiguration in response to local binding events and that are capable of discriminating between chemically similar ions. This discriminatory power has recently been exploited to achieve efficient separation of technologically essential rare-earth elements and relies on finely-tuned electrostatic, thermodynamic, and kinetic properties that remain incompletely understood.

We mobilize infrared spectroscopy as a physical probe of binding site interactions and structure in a variety of signaling metalloproteins and small ion-binding compounds. The latter are used to model the spectroscopic properties of much larger biomolecules. Our results show how the infrared spectrum reports on proteins with different ion binding modes and affinities and, similarly, on the binding configurations of small molecules that are structurally similar but exhibit large differences in ion specificity. These measurements help inform further study of the structural and biophysical consequences of modification to biological and bio-inspired ion-binding structures.