Many Proline Residues in the Extracellular Domain Contribute to Glycine Receptor Function.

Prolines in signaling proteins are of particular interest because they have a range of unique properties that may be critical for function. Here we show that many proline residues in the extracellular domain (ECD) of the glycine receptor are involved in the correct functioning of this ligand-gated ion channel. We explore their role by creating mutant receptors, expressing them in cells, and using fluorescent membrane potential sensitive dye to monitor receptor activity.

The M4 Helix Is Involved in α7 nACh Receptor Function.

Nicotinic acetylcholine receptors (nAChR) are the archetypal members of the pentameric ligand-gated ion channel (pLGIC) family, an important class of cell signaling proteins. In all members of this family, each of the five subunits has four transmembrane α-helices (M1-M4) with M2 lining the pore and then M1 and M3, with M4 outermost and adjacent to the membrane lipids. M4 has a variety of roles: its interaction with neighboring M1 and M3 helices is important for receptor assembly, it can a transmit information on the lipid content of the membrane to the gating mechanism, and it may form a vital link to the extracellular domain via the Cys-loop.