Cadmium exposure and toxicity remain important environmental concerns in the US and this exposure can lead to numerous health issues in children and adults. While it has been observed that Cd(II) can disrupt Ca(II) signaling pathways at the cellular level and recent analysis of the protein data bank reveal that Cd(II) has a binding preference for the oxygen rich Ca(II) binding sites in proteins, little is known about the fundamental thermodynamic forces that drive these interactions. The Spuches lab utilizes isothermal titration calorimetry (ITC) to study the thermodynamics of metal binding to proteins and peptides. We have focused our attention on cardiac troponin C, a calcium binding EF-hand protein involved in cardiac muscle contraction and an attractive model to investigate Cd(II) ion binding. Initial results indicate that one high affinity Cd(II) ion binds to HcTnC and two lower affinity Cd(II) ions bind with positive cooperativity. While it is accepted that the two Cd(II) ions that bind with positive cooperativity are located in the C-domain of the protein, the location of the third high affinity Cd(II) ion(s) is not known. Displacement studies suggest that Cd(II) may be competing for the Ca(II) bound to EF-hand II in the regulatory domain. This model is supported by molecular dynamic simulations of Cd(II) binding to the regulatory domain of Cd(II). These data suggest that while Cd(II) my act as a structural mimic of Ca(II), the thermodynamics of these interactions are quite different and may have deleterious effects by altering subsequent protein interactions.

Heat is on: Investigating the thermodynamics that drive binding of Ca(II) and Cd(II) to human cardiac troponin C

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.