Intrinsically disordered regions couple the ligand binding and kinase activation of Trk neurotrophin receptors
Neurotrophins and their receptors regulate the differentiation, survival, and growth of nerve cells. Despite their central role in the life of neurons, the mechanisms underlying signal transmission into the cell are still not fully understood. According to one of the main hypotheses, after ligand binding the dimer of a Trk neurotrophin receptor undergoes a series of rearrangements that trigger signaling cascades inside the cell. However, structural data supporting this idea have not yet been available. Researchers from the Laboratory of Biomolecular NMR Spectroscopy of the Institute of Bioorganic Chemistry, Russian Academy of Sciences, and the Institute of Biomedicine in Valencia have discovered two states of the transmembrane domain, which, apparently, are responsible for the active and inactive states of the receptor. In addition, it turned out that the extracellular juxtamembrane region is intrinsically disordered. The obtained data suggested that signal transduction is possible if the ligand binds directly to this receptor site, thereby stabilizing it. The work was published in iScience.
june 21, 2022