Protein Structure and Folding
Crystal Structure of Acetylcholine-binding Protein from Bulinus truncatus Reveals the Conserved Structural Scaffold and Sites of Variation in Nicotinic Acetylcholine Receptors*

https://doi.org/10.1074/jbc.M414476200Get rights and content
Under a Creative Commons license
open access

The crystal structure of acetylcholine-binding protein (AChBP) from the mollusk Lymnaea stagnalis is the established model for the ligand binding domains of the ligand-gated ion channel family, which includes nicotinic acetylcholine, 5-hydroxytryptamine (5-HT3), γ-aminobutyric acid (GABA), types A and C, and glycine receptors. Here we present the crystal structure of a remote homolog, AChBP from Bulinus truncatus, which reveals both the conserved structural scaffold and the sites of variation in this receptor family. These include rigid body movements of loops that are close to the transmembrane interface in the receptors and changes in the intermonomer contacts, which alter the pentamer stability drastically. Structural, pharmacological and mutational analysis of both AChBPs shows how 3 amino acid changes in the binding site contribute to a 5-10-fold difference in affinity for nicotinic ligands. Comparison of these structures will be valuable for improving structure-function studies of ligand-gated ion channel receptors, including signal transduction, homology modeling, and drug design.

Cited by (0)

The atomic coordinates and structure factors (code 2BJ0) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ(http://www.rcsb.org/).

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank/EBI Data Bank with accession number(s) CAC69294 and CAC69295.

§

These authors contributed equally to this work.

*

This work was supported by STW (Stichting Technische Weten-schappen), Project BBC6035, by the Netherlands Organization for Research in Chemistry (NWO-CW), Project 98016, and by EU-SPINE. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.