Topological Disposition of Cys 222 in the α-Subunit of Nicotinic Acetylcholine Receptor Analyzed by Fluorescence-Quenching and Electron Paramagnetic Resonance Measurements†

Biochemistry ◽  
1998 ◽  
Vol 37 (13) ◽  
pp. 4680-4686 ◽  
Author(s):  
Jeongah Kim ◽  
Mark G. McNamee
Keyword(s):  
Electron Paramagnetic Resonance ◽  
Fluorescence Quenching ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Paramagnetic Resonance ◽  
Nicotinic Acetylcholine ◽  
Α Subunit ◽  
Electron Paramagnetic

scholarly journals The functional role of the αM4 transmembrane helix in the muscle nicotinic acetylcholine receptor probed through mutagenesis and coevolutionary analyses

2020 ◽  
Vol 295 (32) ◽  
pp. 11056-11067 ◽  
Author(s):  
Mackenzie J. Thompson ◽  
Jaimee A. Domville ◽  
John E. Baenziger
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Site Directed Mutagenesis ◽  
Induced Response ◽  
Independent Manner ◽  
Nicotinic Acetylcholine ◽  
Α Subunit ◽  
Lipid Sensing ◽  
Insight Into

The activity of the muscle-type Torpedo nicotinic acetylcholine receptor (nAChR) is highly sensitive to lipids, but the underlying mechanisms remain poorly understood. The nAChR transmembrane α-helix, M4, is positioned at the perimeter of each subunit in direct contact with lipids and likely plays a central role in lipid sensing. To gain insight into the mechanisms underlying nAChR lipid sensing, we used homology modeling, coevolutionary analyses, site-directed mutagenesis, and electrophysiology to examine the role of the α-subunit M4 (αM4) in the function of the adult muscle nAChR. Ala substitutions for most αM4 residues, including those in clusters of polar residues at both the N and C termini, and deletion of up to 11 C-terminal residues had little impact on the agonist-induced response. Even Ala substitutions for coevolved pairs of residues at the interface between αM4 and the adjacent helices, αM1 and αM3, had little effect, although some impaired nAChR expression. On the other hand, Ala substitutions for Thr422 and Arg429 caused relatively large losses of function, suggesting functional roles for these specific residues. Ala substitutions for aromatic residues at the αM4-αM1/αM3 interface generally led to gains of function, as previously reported for the prokaryotic homolog, the Erwinia chrysanthemi ligand-gated ion channel (ELIC). The functional effects of individual Ala substitutions in αM4 were found to be additive, although not in a completely independent manner. Our results provide insight into the structural features of αM4 that are important. They also suggest how lipid-dependent changes in αM4 structure ultimately modify nAChR function.

scholarly journals Yeast Expression and NMR Analysis of the Extracellular Domain of Muscle Nicotinic Acetylcholine Receptor α Subunit

2002 ◽  
Vol 277 (15) ◽  
pp. 12613-12621 ◽  
Author(s):  
Yun Yao ◽  
Junmei Wang ◽  
Nitnara Viroonchatapan ◽  
Avraham Samson ◽  
Jordan Chill ◽  
...  
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Extracellular Domain ◽  
Yeast Expression ◽  
Nmr Analysis ◽  
Nicotinic Acetylcholine ◽  
Α Subunit

scholarly journals The noncompetitive blocker [3 H]chlorpromazine labels segment M2 but not segment M 1 of the nicotinic acetylcholine receptor α-subunit

FEBS Letters ◽  
1989 ◽  
Vol 253 (1-2) ◽  
pp. 190-198 ◽  
Author(s):  
Jérôme Giraudat ◽  
Jean-Luc Galzi ◽  
Frédéric Revah ◽  
Jean-Pierre Changeux ◽  
Pierre-Yves Haumont ◽  
...  
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine ◽  
Α Subunit
Sign in / Sign up

Export Citation Format

Share Document