Molecular Mechanism of DREAM Dimerization and Interactions with a Non-physiological Ligand Zn2+.

Authors

Maria D. Santiago EstevezFollow

Document Type

Thesis

Degree

Master of Science (MS)

Major/Program

Chemistry

First Advisor's Name

Jaroslava Miksovska

First Advisor's Committee Title

Committee chair

Second Advisor's Name

Francisco Fernandez-Lima

Second Advisor's Committee Title

committee member

Third Advisor's Name

Xiaotang Wang

Third Advisor's Committee Title

committee member

Keywords

DREAM, Neuronal calcium sensors, CBP

Date of Defense

11-13-2019

Abstract

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 Ca²⁺ bound dimer, while in the apo state, a monomer-tetramer equilibrium was observed. A chimeric version of DREAM was prepared by mutating the residues involved in dimerization. DREAM-NCS1 properties were investigated using spectroscopic techniques. These results point towards the role of hydrophobic interactions and salt bridges in stabilizing the dimer and propagating allosteric signals.

Identifier

FIDC008843

Recommended Citation

Santiago Estevez, Maria D., "Molecular Mechanism of DREAM Dimerization and Interactions with a Non-physiological Ligand Zn2+." (2019). FIU Electronic Theses and Dissertations. 4320.
https://digitalcommons.fiu.edu/etd/4320