The research projects in our lab focus on the structure-function-dynamics relationship in two families of proteins: Neuronal calcium sensors, namely Downstream Regulatory Element Antagonist Modulator (DREAM), and hexacoordinate vertebrate globins Neuroglobin and Cytoglobin,using state-of-the-art spectroscopic techniques.
1) Mechanism of signal recognition and transduction in calcium binding proteins.
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Neuronal calcium sensor proteins represent a distinct family of EF-hand calcium transducers that are involved in regulation of several aspects of neuronal function. Downstream Regulatory Element Antagonist Modulator (DREAM), also known as calsenilin or potassium channel interacting protein-3 (KChIP-3), is a multifunctional protein that directly controls the activity and assembly of the potassium voltage channel, interacts with presenilin and APP processing, and is responsible for repression of gene transcription by binding to the DRE sequence of DNA. In order to fully understand the most basic aspects of neuronal regulation by Ca2+ ions, we use time resolved techniques including time-resolved fluorescence and polarization and mass spectrometry approaches to characterize the conformational changes in DREAM and understand the mechanism of DREAM ineractions with various intracellular partners.
2) Conformational dynamics in vertebrate hexa-coordinate hemoglobins
Two hexa-coordinate heme proteins have recently been discovered in humans and other vertebrates. Neuroglobin (Ngb) has been found predominantly in brain tissue where it plays important role in the protections of neuronal tissue under conditions of hypoxia and ischemic stress. Cytoglobin (Cygb) is found in connective tissue of body organs such as including lung, heart and brain. Physiological role of this protein has not been fully established, however, several evidences point out to its role in protecting cells against oxidative stress. Cygb was also associated with several types of cancer including sporadic non small cell lung cancer, and head and neck cancer. Our long term goal is to unravel the physiological function of Ngb and to understand the structure-function relationship in the family of hexa-coordinate globins. Our specific goals are i) to determine the time profile and energetic of conformational changes associated with ligand (O2 and CO) binding to Ngb and Cygb and ii) to determine flexibility of the protein structure as a function of the ligand binding to hxHb.