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Experimental determination of the vertical alignment between the second and third transmembrane segments of muscle nicotinic acetylcholine receptors
- Source :
- Journal of Neurochemistry. 125:843-854
- Publication Year :
- 2013
- Publisher :
- Wiley, 2013.
-
Abstract
- Nicotinic acetylcholine receptors (nAChR) are members of the Cys-loop ligand-gated ion channel superfamily. Muscle nAChR are heteropentamers that assemble from two α, and one each of β, γ, and δ subunits. Each subunit is composed of three domains, extracellular, transmembrane and intracellular. The transmembrane domain consists of four α-helical segments (M1–M4). Pioneering structural information was obtained using electronmicroscopy of Torpedo nAChR. The recently-solved X-ray structure of the first eukaryotic Cys-loop receptor, a truncated (intracellular domain missing) glutamate-gated chloride channel α (GluClα)showed the same overall architecture . However, a significant difference with regard to the vertical alignment between the channel-lining segment M2 and segment M3 was observed. Here we used functional studies utilizing disulfide trapping experiments in muscle nAChR to determine the spatial orientation between M2 and M3. Our results are in agreement with the vertical alignment as obtained when using the GluClα structure as a template to homology model muscle nAChR, however, they cannot be reconciled with the current Torpedo nAChR model. The vertical M2–M3 alignments as observed in X-ray structures of prokaryotic Gloeobacter violaceus ligand-gated ion channel (GLIC) and GluClα are in agreement. Our results further confirm that this alignment in Cys-loop receptors is conserved between prokaryotes and eukaryotes.
- Subjects :
- Patch-Clamp Techniques
GLIC
Receptors, Nicotinic
Biology
Torpedo
Biochemistry
Protein Structure, Secondary
Article
law.invention
Mice
Xenopus laevis
Cellular and Molecular Neuroscience
Species Specificity
Chloride Channels
law
Animals
Disulfides
Homology modeling
Caenorhabditis elegans Proteins
Ion channel
Acetylcholine receptor
Muscles
Transmembrane protein
Protein Structure, Tertiary
Transmembrane domain
Nicotinic agonist
Mutation
Oocytes
Biophysics
Female
Subjects
Details
- ISSN :
- 00223042
- Volume :
- 125
- Database :
- OpenAIRE
- Journal :
- Journal of Neurochemistry
- Accession number :
- edsair.doi.dedup.....326c212bf9a5326ced5a176f6d21a556