ACETYLCHOLINE BINDING PROTEIN (AChBP): A Secreted Glial Protein That Provides a High-Resolution Model for the Extracellular Domain of Pentameric Ligand-Gated Ion Channels

Abstract

▪ Abstract Acetylcholine binding protein (AChBP) has recently been identified from molluskan glial cells. Glial cells secrete it into cholinergic synapses, where it plays a role in modulating synaptic transmission. This novel mechanism resembles glia-dependent modulation of glutamate synapses, with several key differences. AChBP is a homolog of the ligand binding domain of the pentameric ligand-gated ion-channels. The crystal structure of AChBP provides the first high-resolution structure for this family of Cys-loop receptors. Nicotinic acetylcholine receptors and related ion-channels such as GABAA, serotonin 5HT3, and glycine can be interpreted in the light of the 2.7 Å AChBP structure. The structural template provides critical details of the binding site and helps create models for toxin binding, mutational effects, and molecular gating.