|Name||Mr. Samiol Azam|
|Organization or Institution||Florida Int University|
Cadmium Associates to DREAM and Alters Its Interactions with Intracellular Partners
Samiol Azam and Jaroslava Miksovska
Florida Int University
Cadmium is a toxic metal that has received tremendous environmental and health concerns. Cadmium exposure has been associated with different cancers, Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease. However, the underlying mechanism through which cadmium exert its toxic effect has not demystified yet. Studies have demonstrated that cadmium accumulates in the hippocampus, the part of the brain involved in memory and learning processes. Here, we show that cadmium associates to a neuronal calcium sensor protein DREAM, a protein expressed in the hippocampus region of the brain and has been associated with memory and learning processes. Our data demonstrate that cadmium associates to EF-hands in DREAM with an equilibrium affinity higher than that determined for Ca2+. Based on the Trp 169 emission and CD spectra, we show that cadmium association triggers changes in the secondary and tertiary structures of the protein that is analogous to the previously observed Ca2+ association to DREAM. The hydrophobic cavity in the C-terminal domain of DREAM is more solvent exposed in the presence of cadmium as determined using a hydrophobic probe 1,8-ANS. Cadmium associating also alters DREAM’s interactions with intracellular partners. We titrated fluorescently labeled peptide presenilin-1 helix-9 “PS1HL9”, Kv4.3(2-22) “site-1”, and Kv4.3(70-90) “site-2” against Cd2+-bound DREAM in anisotropy measurements. Titration data show that Cd2+-bound DREAM has similar affinity for PS1HL9 as Ca2+-bound DREAM; likewise, Cd2+-bound DREAM has an analogous binding affinity for site-1 and site-2 as Ca2+-bound DREAM. The isothermal titration calorimetry (ITC) data reveal that two cadmium ions bind to DREAM endothermically and through an entropy-driven process. These results suggest that DREAM and possibly other neuronal calcium sensors could bind cadmium and cadmium association to DREAM could provide insight into cadmium-induced toxicity.