ISSN:
1432-1017
Keywords:
Ion channel
;
Nicotinic receptor
;
α-helix bundle
;
Molecular modelling
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Physics
Notes:
Abstract The ion channel of the nicotinic acetylcholine receptor (nAChR) is believed to be lined by transmembrane M2 helices. A “4-8-12” sequence motif, comprising serine (S) or threonine (T) residues at positions 4, 8 and 12 of M2, is conserved between different members, anion and cation selective, of the nAChR superfamily. Parallel bundles of 4-8-12 motif-containing helices are considered as simplified models of ion channels. The relationship between S and T sidechain conformations and channelion interactions is explored via evaluation of interaction energies of K+ and of Cl− ions with channel models. Energy calculations are used to determine optimal ξ2 (Cα-C\-Oγ-Hγ) values in the presence of K+ or Cl− ions. 4-8-12 motif-containing bundles may form favourable interactions with either cations or anions, dependent upon the ξ2 values adopted. Parallel-helix and tilted-helix bundles are considered, as are heteromeric models designed to mimic the Torpedo nAChR. The main conclusion of the study is that conformational flexibility at ξ2 enables both S and T residues to form favourable interactions with anions or cations. Consequently, there is apparently no difference between S and T residues in their interactions with permeant ions, which suggests that the presence of T vs. S residues within the 4-8-12 motif is not a major mechanism whereby anion/cation selectivity may be generated. The implications of these studies with respect to more elaborate models of nAChR and related receptors are considered.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00185123
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