Channels: Rotamers affect ion conductance

Abstract

A major determinant of the ion flux rate through acetylcholine receptors is a ring of five residues, four glutamates and a glutamine, at the channel’s cytoplasmic mouth. The glutamates adopt alternate rotamer conformations so that only two directly affect channel conductance.

Figure

Cys-loop receptor channel structure illustrated using the GluCl channel structure (PDB: 3RIF). (A) Cartoon representation of the GluCl channel subunit secondary structure. The channel lumen would be on the left. The M2 membrane-spanning segment is in dark orange. The position of the intermediate ring residue is indicated in gray near the cytoplasmic end of the M2 segment. (B) View from the cytoplasmic channel mouth up the channel. Channel lumen is indicated by the pale blue circle in the center. Muscle-type AChRs contain four subunits, two α (light orange) and one each of β (green), δ (blue) and ε (cyan). The channel is lined by the five M2 segments. The position of the other membrane-spanning segments is indicated on one of the α subunits. (C) Close up view of the cytoplasmic end of the channel surrounded by the five M2 segments. The intermediate ring residues in the AChR have been inserted into the GluCl structure in stick representation using Pymol software: α, β and δ have a glutamate and ε has a glutamine. For illustrative purposes the glutamate rotamer conformation in β and δ faces the carboxylates towards the channel, whereas in the α subunits the carboxylates face away from the channel lumen. (D) Side view of the cytoplasmic end of the channel. The front two subunits, α and ε, have been removed to visualize the channel. Intermediate ring side chains are shown in stick representation. Figure generated using Pymol. Subunit color scheme is maintained throughout the figure.