The role of charged residues in independent glycine receptor folding domains for intermolecular interactions and ion channel function

摘要: Glycine receptor (GlyR) truncations in the intracellular TM3-4 loop, documented patients suffering from hyperekplexia and mouse mutant oscillator, lead to non-functionality of GlyRs. The missing part that contains TM4 C-terminal sequences is essential for pentameric arrangements. In vitro co-expressions GlyRα1-truncated N-domains C-domains were able restore ion channel function. An ionic interaction between both domains was hypothesized as underlying mechanism. Here, we analysed proposed GlyR N- using constructs with either positively or negatively charged N-termini. Charged residues at N-terminus C-domain did interfere surface expression particular, presence led significantly decreased Presence positive charges resulted reduced maximal currents possibly a result repulsion domains. If tagged by myc-epitope, low current amplitudes detected. Intrinsic myc-epitope N-terminal ends most probably induce intramolecular interactions. These interactions might hinder close proximity N-domains, which prerequisite functional configurations. remaining basic subdomains TM3 4 sufficient domain complementation formation. Thus, these forming α-helical elements an portal represent attractants incoming chloride ions interact phospholipids thereby stabilizing conformation allows opening.