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Structural basis of open channel block in a prokaryotic pentameric ligand-gated ion channel


Hilf, R J C; Bertozzi, C; Zimmermann, I; Reiter, A; Trauner, D; Dutzler, R (2010). Structural basis of open channel block in a prokaryotic pentameric ligand-gated ion channel. Nature Structural and Molecular Biology, 17(11):1330-1336.

Abstract

The flow of ions through cation-selective members of the pentameric ligand-gated ion channel family is inhibited by a structurally diverse class of molecules that bind to the transmembrane pore in the open state of the protein. To obtain insight into the mechanism of channel block, we have investigated the binding of positively charged inhibitors to the open channel of the bacterial homolog GLIC by using X-ray crystallography and electrophysiology. Our studies reveal the location of two regions for interactions, with larger blockers binding in the center of the membrane and divalent transition metal ions binding to the narrow intracellular pore entry. The results provide a structural foundation for understanding the interactions of the channel with inhibitors that is relevant for the entire family.

Abstract

The flow of ions through cation-selective members of the pentameric ligand-gated ion channel family is inhibited by a structurally diverse class of molecules that bind to the transmembrane pore in the open state of the protein. To obtain insight into the mechanism of channel block, we have investigated the binding of positively charged inhibitors to the open channel of the bacterial homolog GLIC by using X-ray crystallography and electrophysiology. Our studies reveal the location of two regions for interactions, with larger blockers binding in the center of the membrane and divalent transition metal ions binding to the narrow intracellular pore entry. The results provide a structural foundation for understanding the interactions of the channel with inhibitors that is relevant for the entire family.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2010
Deposited On:26 Jan 2011 16:07
Last Modified:05 Apr 2016 14:27
Publisher:Nature Publishing Group
ISSN:1545-9985
Publisher DOI:https://doi.org/10.1038/nsmb.1933
PubMed ID:21037567

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