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.

Mechanism of Signal Recognition and Transduction in Calcium-Binding Proteins

Neuronal calcium sensor (NCS) proteins constitute a distinct family of EF-hand calcium-binding proteins that translate changes in intracellular Ca²⁺ concentrations into cellular responses, thereby regulating diverse 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 neuronal calcium sensor involved in several cellular processes. DREAM directly regulates the activity and assembly of voltage-gated potassium channels, interacts with presenilin and components of the amyloid precursor protein (APP) processing pathway, and functions as a transcriptional repressor by binding to downstream regulatory element (DRE) sequences in DNA.

To understand the molecular mechanisms underlying neuronal regulation by Ca²⁺, we combine time-resolved biophysical approaches, including time-resolved fluorescence and fluorescence polarization, with mass spectrometry. These complementary techniques allow us to characterize Ca²⁺-dependent conformational changes in DREAM and elucidate the molecular mechanisms governing its interactions with diverse intracellular partners. Our goal is to define how Ca²⁺ binding is translated into structural and functional changes that regulate DREAM activity and, ultimately, neuronal signaling.

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.