Calorimetric and Spectroscopic Tools Used to Study Pb2+ Binding to Human Cardiac Troponin C: A Mini-Review

Abstract

Toxic metal exposure is linked to a variety of health issues including cardiovascular disease and diabetes. It is known that toxic metals are capable of mimicking essential metals for binding sites in proteins. It is also known that both divalent cadmium (Cd(II)) and lead (Pb(II)) can disrupt Ca(II) signaling pathways. However, little else is known about how this happens at the molecular level. Research in the Spuches Lab is geared towards understanding metal toxicity from a structural and thermodynamic perspective. Previous studies have focused on Cd(II) binding to human Cardiac troponin C (hcTnC), a Ca(II) binding protein that is responsible for heart muscle contraction. Future studies will include Pb(II) binding to wild-type and C35A/C84A N-domain hcTnC, a protein that has been well characterized in the Ca(II) and Cd(II) bound states. Both calorimetric and spectroscopic techniques have been used in the Spuches lab to investigate these interactions. This mini-review will discuss the environmental and health impact of Pb(II) toxicity and the techniques used to study this harmful metals interactions with various target proteins such as hcTnC. These techniques include but are not limited to Isothermal titration Calorimetry (ITC) and circular dichroism (CD) spectroscopy. Taken together, one can obtain insight Pb(II) toxicity at the molecular level.