Accepted_test

Neurotrophin receptors: the transmembrane domain as a key player of the receptor activation and a target for antidepressants

by Goncharuk Sergey | Kot Erik | Mineev Konstantin | Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow, Russia | Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow, Russia | Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow, Russia

Abstract ID: 193

Event: BGRS-abstracts

Sections: [Sym 3] Section “Structural biology of proteins nucleic acids and membranes”

Neurotrophins and their receptors are key players in the development of the vertebrate nervous system and therefore represent a target for the treatment of various neurodegenerative disorders and cancers. The neurotrophins signal through two types of cellular receptors — the Trk family of tyrosine kinases and the p75NTR. To elucidate the mechanism of receptor activation and thus to facilitate rational drug design, the three-dimensional structures are required. To date, the structures of extracellular and intracellular domains of P75 and Trk receptors have been obtained, including ligand-binding state, however the activation process is still uncovered. The blind spot is the structure of transmembrane domains in different states. Here we present the structures of transmembrane domain of neurotrophin receptors in active and inactive states, and study the interaction of TrkB with antidepressants.