Event Title

Calcium Sensor DREAM is a Novel Neuronal Target for Zinc

Presenter Information

Enzo Leon

Department

Biochemistry

Faculty Advisor

Jaroslava Miksovska

Start Date

29-9-2020 9:00 AM

End Date

29-9-2020 10:00 AM

Abstract

Downstream Regulatory Element Antagonist Modulator (DREAM) is protein that is found naturally in the brain. DREAM falls within a particular family of neuronal calcium sensor (NCS) proteins: class E, referring to KChIPs. DREAM has been proposed to be involved in various processes such as memory, learning, pain sensitivity, regulation of kinetics of potassium channels and gene transcription. In addition, this protein has been linked to neuropathological diseases such as Alzheimer’s and Huntington’s disease. DREAM can carry out several intracellular functions due to its interactions with numerous intracellular partners that are regulated by a secondary messenger Ca2+. Previous studies in our group have shown that calcium binding sites in DREAM are not calcium specific and can bind other metals with an affinity that is superior to that for Ca2+. Here we tested if DREAM can be an intracellular target for zinc as this metal has been recently shown to bind to recoverin, a member of the NCS family [Permyakov, S. E. et al., 2003] . The fluorescence emission results indicate that Zn2+ interacts with DREAM, in both apo- and Ca2+ bound form, with a relatively high affinity, Kd ≈ 5M, triggering changes in the protein tertiary structure. Adding Zn2+ to 1,8 ANS-DREAM complex increases the 1,8 ANS fluorescence intensity suggesting an increased exposure of hydrophobic sites on the protein surface in the presence of Zn2+. Also, Zn2+ addition to DREAM results in the increase in the protein’s -helical content proposing that Zn2+ binding to apo DREAM promotes protein stability. These results indicate that DREAM and other neuronal calcium sensors may interact with zinc and such interactions may be involved in zinc neuropathology.

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Sep 29th, 9:00 AM Sep 29th, 10:00 AM

Calcium Sensor DREAM is a Novel Neuronal Target for Zinc

Downstream Regulatory Element Antagonist Modulator (DREAM) is protein that is found naturally in the brain. DREAM falls within a particular family of neuronal calcium sensor (NCS) proteins: class E, referring to KChIPs. DREAM has been proposed to be involved in various processes such as memory, learning, pain sensitivity, regulation of kinetics of potassium channels and gene transcription. In addition, this protein has been linked to neuropathological diseases such as Alzheimer’s and Huntington’s disease. DREAM can carry out several intracellular functions due to its interactions with numerous intracellular partners that are regulated by a secondary messenger Ca2+. Previous studies in our group have shown that calcium binding sites in DREAM are not calcium specific and can bind other metals with an affinity that is superior to that for Ca2+. Here we tested if DREAM can be an intracellular target for zinc as this metal has been recently shown to bind to recoverin, a member of the NCS family [Permyakov, S. E. et al., 2003] . The fluorescence emission results indicate that Zn2+ interacts with DREAM, in both apo- and Ca2+ bound form, with a relatively high affinity, Kd ≈ 5M, triggering changes in the protein tertiary structure. Adding Zn2+ to 1,8 ANS-DREAM complex increases the 1,8 ANS fluorescence intensity suggesting an increased exposure of hydrophobic sites on the protein surface in the presence of Zn2+. Also, Zn2+ addition to DREAM results in the increase in the protein’s -helical content proposing that Zn2+ binding to apo DREAM promotes protein stability. These results indicate that DREAM and other neuronal calcium sensors may interact with zinc and such interactions may be involved in zinc neuropathology.