Reet Link "Ligand binding, allosteric modulation and constitutive activity of melanocortin-4 receptors"

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View all other units

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Date:

25.08.2020 - 11:15

On 25 August at 11:15 Reet Link will defend her thesis "Ligand binding, allosteric modulation and constitutive activity of melanocortin-4 receptors" for obtaining the degree of Doctor of Philosophy (Chemistry).

Supervisors:
Sergei Kopantšuk (PhD), UT Institute of Chemistry
Prof. Ago Rinken (PhD), UT Institute of Chemistry

Opponent:
Prof. Dr Janis Klovins (PhD), Latvian Biomedical Research and Study Centre, Latvia.

Summary:
Biochemical studies are often targeted at protein-related interactions as they play a key role in the regulation of biochemical processes in living organisms. Membrane proteins called receptors regulate physiologic and metabolic processes by acting as mediators of extracellular signals. Specific chemical signals, called ligands, can initiate the signal transduction by binding to the receptors. The largest receptor family in mammals, G protein-coupled receptors (GPCRs), mediate the extracellular signal into the cell mainly through intracellular G proteins that activate further signaling pathways. Melanocortin-4 (MC4) receptors are GPCRs expressed mainly in the central nervous system, which signaling pathways regulate several important functions in the body, including energy homeostasis, eating behavior and sexual functions. Therefore, these receptors are of great interest for drug development companies. The signal transduction of MC4 receptors is a complex dynamic process, where much information remains yet elusive. The general aim of this dissertation was to obtain additional information about the signal transduction of MC4 receptors, in particular their ligand binding, allosteric modulation and constitutive activity. To achieve the general goal of the work, several specific tasks were set, which included the development of fluorescence-based ligand binding and functional methods for MC4 receptors; development and characterization of new MC4 receptor fluorescent ligands; and characterization of the modulation of MC4 receptor signaling by different metal ions. Fluorescence anisotropy (FA) based ligand binding assay and Förster resonance energy transfer (FRET) based functional assays were used for the MC4 receptors studies in this work. Using the fluorescence-based methods it was found that endogenous Zn2+ and Cu2+ ions allosterically modulate that ligand binding to MC4 receptors. In addition, Zn2+ and Cu2+ regulated the constative activity of MC4 receptors by increasing or reducing its signaling, respectively. These physiologically important metal ions can also be important modulators of the signal transduction of other GPCRs.

Link of defense Microsoft Teams

Organizer:

Heili Kasuk

Location:

Ravila 14A–1020 and via videobridge

URL:

https://dspace.ut.ee/handle/10062/68501

Event category:

Defence

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7 The inaugural lecture by Gholamreza Anbarjafari, UT Professor of of Computer Vision The Exhibition "The enchanting art of stone cutting. Morgenstern 250" Aarne Maasik’s Photos of Tartu Cathedral Estonia's National University 100: Photo exhibition “Put on Your Thinking Cap! The Hundred Faces of the University of Tartu”	8 The Exhibition "The enchanting art of stone cutting. Morgenstern 250" Aarne Maasik’s Photos of Tartu Cathedral Estonia's National University 100: Photo exhibition “Put on Your Thinking Cap! The Hundred Faces of the University of Tartu”	9 Kadi Luht-Kallas „Risk-taking behaviour: Relationship with personality and markers of heritability, and an intervention to prevent unintentional injury“ The Exhibition "The enchanting art of stone cutting. Morgenstern 250" Aarne Maasik’s Photos of Tartu Cathedral Estonia's National University 100: Photo exhibition “Put on Your Thinking Cap! The Hundred Faces of the University of Tartu”	10 Larisa Ivanova “Design of active compounds against neurodegenerative diseases” The Exhibition "The enchanting art of stone cutting. Morgenstern 250" Aarne Maasik’s Photos of Tartu Cathedral Estonia's National University 100: Photo exhibition “Put on Your Thinking Cap! The Hundred Faces of the University of Tartu”	11 The Exhibition "The enchanting art of stone cutting. Morgenstern 250" Aarne Maasik’s Photos of Tartu Cathedral Estonia's National University 100: Photo exhibition “Put on Your Thinking Cap! The Hundred Faces of the University of Tartu”	12 The Exhibition "The enchanting art of stone cutting. Morgenstern 250" Aarne Maasik’s Photos of Tartu Cathedral Estonia's National University 100: Photo exhibition “Put on Your Thinking Cap! The Hundred Faces of the University of Tartu”	13 The Exhibition "The enchanting art of stone cutting. Morgenstern 250" Aarne Maasik’s Photos of Tartu Cathedral Estonia's National University 100: Photo exhibition “Put on Your Thinking Cap! The Hundred Faces of the University of Tartu”
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Reet Link "Ligand binding, allosteric modulation and constitutive activity of melanocortin-4 receptors"

September