The pore domain of the nicotinic acetylcholine receptor: molecular modeling, pore dimensions, and electrostatics
The pore domain of the nicotinic acetylcholine receptor has been modeled as a bundle of five kinked M2 helices. Models were generated via molecular dynamics simulations incorporating restraints derived from 9-Å resolution cryoelectron microscopy data (Unwin, 1993; 1995), and from mutagenesis data th...
| প্রধান লেখক: | , , |
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| অন্যান্য লেখক: | |
| বিন্যাস: | Journal article |
| ভাষা: | English |
| প্রকাশিত: |
Elsevier
1996
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| বিষয়গুলি: |
| সংক্ষিপ্ত: | The pore domain of the nicotinic acetylcholine receptor has been modeled as a bundle of five kinked M2 helices. Models were generated via molecular dynamics simulations incorporating restraints derived from 9-Å resolution cryoelectron microscopy data (Unwin, 1993; 1995), and from mutagenesis data that identify channel-lining side chains. Thus, these models conform to current experimental data but will require revision as higher resolution data become available. Models of the open and closed states of a homopentameric α7 pore are compared. The minimum radius of the closed-state model is less than 2 Å; the minimum radius of the open-state models is ∼6 Å. It is suggested that the presence of "bound" water molecules within the pore may reduce the effective minimum radii below these values by up to ∼3 Å. Poisson-Boltzmann calculations are used to obtain a first approximation to the potential energy of a monovalent cation as it moves along the pore axis. The differences in electrostatic potential energy profiles between the open-state models of α7 and of a mutant of α7 are consistent with the experimentally observed change in ion selectivity from cationic to anionic. Models of the open state of the heteropentameric <em>Torpedo</em> nicotinic acetylcholine receptor pore domain are also described. Relatively small differences in pore radius and electrostatic potential energy profiles are seen when the <em>Torpedo</em> and α7 models are compared. |
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