Premium
Cover Picture: Acetylcholine Promotes Binding of α‐Conotoxin MII at α 3 β 2 Nicotinic Acetylcholine Receptors (ChemBioChem 3/2014)
Author(s) -
Sambasivarao Somisetti V.,
Roberts Jessica,
Bharadwaj Vivek S.,
Slingsby Jason G.,
Rohleder Conrad,
Mallory Chris,
Groome James R.,
McDougal Owen M.,
Maupin C. Mark
Publication year - 2014
Publication title -
chembiochem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201490004
Subject(s) - acetylcholine , chemistry , acetylcholine receptor , biophysics , conotoxin , voltage clamp , ion channel , nicotinic acetylcholine receptor , nicotinic agonist , torpedo , receptor , biochemistry , stereochemistry , biology , venom , pharmacology , membrane potential
The cover picture shows the binding of α‐conotoxin MII to the C‐loop of an α 3 β 2 neuronal acetylcholine receptor residing in the post‐synaptic phospholipid bilayer, which comprises a 3:1:1 ratio of POPC, POPA, and cholesterol. Docking studies and voltage clamp experiments show that the presence of acetylcholine in the C‐loop region enhances the binding of toxin, slowing its washout. These observations indicate that α‐conotoxin MII might preferentially target active synaptic clefts, which would be an evolutionary advantage. On p. 413 ff. , O. M. McDougal, C. M. Maupin, et al. describe the creation of two heteropentameric α 3 β 2 neuronal acetylcholine receptor homology models that were used in docking studies of acetylcholine, α‐conotoxin, and both neurotransmitter and toxin to the various C‐loop regions (i.e., α 3 –β 2 , β 2 –α 3 , and β 2 –β 2 ). Subsequent voltage clamp experiments confirmed that the presence of acetylcholine enhanced the binding of toxin prolonging its effect on the ligand‐gated ion channel. (Cover art designed by C.M.M.).