Physical Sciences and Mathematics Commons^™

Allosteric Mechanism On Dream Dimerization And Impact On Its Interactions With Divalent Metal Zn2+, Maria D. Santiago Estevez

FIU Electronic Theses and Dissertations

DREAM belongs to the NCS family, and it is involved in several physiological processes mediated by Ca²⁺ association, which produces changes in its oligomerization state. The mechanism of how Ca²⁺ binds to DREAM remains unknown. A kinetic study of the binding of Ca²⁺ to DREAM suggested that DREAM dimerization is a two-step process, the first step( τ₁= 8±0.1ms) is associated with the binding of Ca²⁺ to the monomer, while the second step (τ₂ = 3.6 ±0.4 s ) corresponds to a conformation relaxation that leads to the dimerization. Furthermore, by analyzing the fast …

Molecular Mechanism Of Dream Dimerization And Interactions With A Non-Physiological Ligand Zn2+., Maria D. Santiago Estevez

FIU Electronic Theses and Dissertations

Downstream Regulatory Element Antagonist Modulator (DREAM) belongs to the family of neuronal calcium sensor proteins and it is involved in several processes in the brain.

Zinc has been shown to bind to recoverin, with submillimolar affinity. Based on the high sequence homology between the NCS family, it is proposed that DREAM can also serve as an intracellular target for Zn²⁺. Fluorescence and CD studies confirm that zinc binds to DREAM with a of K_d = 4 µM, triggering changes in the proteins’ tertiary structure.

The calcium association to DREAM leads to the formation of a Ca^{2+ …}

Consequences Of Non-Physiological Ligands Binding To Dream On Its Secondary And Tertiary Structures And Interactions With Intracellular Partners., Samiol Azam

FIU Electronic Theses and Dissertations

Downstream regulatory antagonist modulator (DREAM) is 29 kDa neuronal calcium sensor (NCS) protein which is expressed in the hippocampus of the brain. DREAM is a multifunctional protein which is involved in a wide spectrum of biological processes, including regulation of potassium current in brain, modulation of pain, presenilin-1 processing, regulation of memory and learning. Exposure to toxic metals such as Pb2+ and Cd2+ have been associated with different types of neurodegenerative diseases. However, how these toxic metals induce neurotoxicity remains an active area of research. In this study, utilizing a combination of spectroscopic and calorimetric techniques, we demonstrated binding of …

Conformational Dynamics And Stability Associated With Magnesium Or Calcium Binding To Dream In The Regulation Of Interactions Between Dream And Dna Or Presenilins, Khoa Ngoc Pham

FIU Electronic Theses and Dissertations

Downstream regulatory element antagonist modulator (DREAM) is involved in various interactions with targets both inside and outside of the nucleus. In the cytoplasm, DREAM interacts with the C-terminal fragments of presenilins to facilitate the production of β-amyloid plaques in Alzheimer’s disease. In the nucleus, Ca²⁺ free DREAM directly binds to specific downstream regulatory elements of prodynorphin/c-fos gene to repress the gene transcription in pain modulation. These interactions are regulated by Ca²⁺ and/or Mg²⁺ association at the EF-hands in DREAM. Therefore, understanding the conformational dynamics and stability associated with Ca²⁺ and/or Mg²⁺ binding to DREAM …