Unraveling the complex signaling behavior of neurotransmitters and their receptors in the brain
Year: 2020
Type: dissertation
Abstract: G protein-coupled receptors (GPCRs) are the main acceptors of neurotransmitters, and thus play an important role in communication between neurons. Because of this they are an attractive drug target for multiple neurodegenerative and neuropsychiatric disorders. The primary function of GPCRs is to initiate diverse intracellular signaling cascades in response to extracellular events, like neurotransmitter binding. Despite the wealth of available biochemical data, the structural foundations of GPCR activity remain poorly understood. Such insights would not only expand our knowledge of those receptors, but also facilitate the design of safer and more efficient drugs. Here, using several computational approaches, we propose structural mechanisms that explain GPCR in vitro data. We unravel features GPCR functionality at multiple levels of action including ligandreceptor interactions, allosteric signal transmission as well as posttranslational modifications. Our results identify phenomena potentially conserved among GPCRs that advance our understanding of this relevant receptor family.
Author: Tomasz Maciej Stępniewski
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3016059609