Thermal unfolding of a mammalian pentameric ligand-gated ion channel proceeds at consecutive, distinct steps

Abstract

Background: The 5-hydroxytryptamine receptor (5-HT3R) is a prototypical pentameric ligand-gated ion channel. Results: The receptor's thermal stability was investigated in native plasma membranes, in detergent solution, and in reconstituted lipid bilayers. Conclusion: Unfolding of the 5-HT3R occurs via hierarchical, consecutive structural transitions, which can be distinguished experimentally. Significance: Our findings serve as an important base to create receptors of increased stability for structural/functional studies. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.