PhD defense: Zigmantas Toleikis

Structure of the leptin receptor related with obesity

Supervisor: Associate Professor Kaare Teilum

Assessment Committee:
Associate Professor Vytautas Smirnovas, Vilnius University
Principal Scientist Jens Breinholdt, Novo Nordisk A/S
Professor Jakob R. Winther, BIO (Chairman)

Abstract:
Leptin acts through leptin receptor and regulates body fat store and expenditures, immune system, bone formation and fertility. The details of leptin action mechanism and receptor activation is still elusive and a high resolution structure of the leptin receptor in an apo and holo states would help to better understand the receptor activation. We have solved the structures of a few leptin receptor domains and characterized the interaction using NMR spectroscopy. In addition, alternative low populated states were detected for the leptin receptor domains using high pressure NMR spectroscopy. These states might play an important role for receptor activation in a living cell. Finally, we describe the structure formation of the conserved WSXWS motif, which is important for receptor folding and might work as a molecular switch for receptor activation.