Maria J. Santiago Estevez and Jaroslava Miksovska Department of Chemistry and Biochemistry, Florida International University Neuronal calcium sensors regulate several physiological processes in the brain and are linked to numerous pathological conditions such as autism, Parkinson and Alzheimer disease. Downstream regulatory element antagonist modulator (DREAM) is among the neuronal calcium sensor family, it is an EF-hand protein highly expressed in the central nervous system in various areas such as the hippocampus and the neural cortex. It is responsible for regulating the kinetics of potassium channels, gene expression, calcium homeostasis and enzymatic activity of presenilin. The characterization of the metal-binding properties of DREAM and how it affects DREAM structure and DREAM interactions with effector proteins is fundamental to understand its biological function. Essential metals like Mg2+, Zn2+ and Ca2+ play extremely important roles in biological processes through direct interactions with proteins. DREAM carries out two Ca2+ binding EF hands and one Mg2+ binding EF hand, however, DREAM binding to other biologically significant metals is not very well known. Interactions of DREAM with Zn2+ have been monitored by using intrinsic and extrinsic fluorescent probes. Data shows that Zn2+ associates to DREAM with Kd ∼ 200 μM. Zn2+ and it does not compete for the same binding site as Ca2+ as the changes in the protein tertiary structure are distinct from those observed upon Ca2+association. Considering increased concentration of Zn2+ in neuronal tissue (150 - 200 μM), these results point towards the potential role of Zn2+ in modulating DREAM interactions with other intracellular proteins.