NDLI: Molecular Dissection of Cl−-selective Cys-loop Receptor Points to Components That Are Dispensable or Essential for Channel Activity*

Content Provider	PubMed Central
Author	Bar-lev, Dekel D. Degani-katzav, Nurit Perelman, Alexander Paas, Yoav
Copyright Year	2011
Abstract	Cys-loop receptors are pentameric ligand-gated ion channels (pLGICs) that bind neurotransmitters to open an intrinsic transmembrane ion channel pore. The recent crystal structure of a prokaryotic pLGIC from the cyanobacterium Gloeobacter violaceus (GLIC) revealed that it naturally lacks an N-terminal extracellular α helix and an intracellular domain that are typical of eukaryotic pLGICs. GLIC does not respond to neurotransmitters acting at eukaryotic pLGICs but is activated by protons. To determine whether the structural differences account for functional differences, we used a eukaryotic chimeric acetylcholine-glutamate pLGIC that was modified to carry deletions corresponding to the sequences missing in the prokaryotic homolog GLIC. Deletions made in the N-terminal extracellular α helix did not prevent the expression of receptor subunits and the appearance of receptor assemblies on the cell surface but abolished the capability of the receptor to bind α-bungarotoxin (a competitive antagonist) and to respond to the neurotransmitter. Other truncated chimeric receptors that lacked the intracellular domain did bind ligands; displayed robust acetylcholine-elicited responses; and shared with the full-length chimeric receptor similar anionic selectivity, effective open pore diameter, and unitary conductance. We suggest that the integrity of the N-terminal α helix is crucial for ligand accommodation because it stabilizes the intersubunit interfaces adjacent to the neurotransmitter-binding pocket(s). We also conclude that the intracellular domain of the chimeric acetylcholine-glutamate receptor does not modulate the ion channel conductance and is not involved in positioning of the pore-lining helices in the conformation necessary for coordinating a Cl− ion within the intracellular vestibule of the ion channel pore.
Related Links	http://dx.doi.org/10.1074/jbc.M111.282715
Starting Page	43830
File Format	PDF
ISSN	1083351X
e-ISSN	1083351X
Journal	The Journal of Biological Chemistry
Issue Number	51
Volume Number	286
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2011-12-23
Access Restriction	Open
Rights Holder	American Society for Biochemistry and Molecular Biology
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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