A model of the closed form of the nicotinic acetylcholine receptor m2 channel pore.
The nicotinic acetylcholine receptor is a neurotransmitter-gated ion channel in the postsynaptic membrane. It is composed of five homologous subunits, each of which contributes one transmembrane helix--the M2 helix--to create the channel pore. The M2 helix from the delta subunit is capable of forming a channel by itself. Although a model of the receptor was recently proposed based on a low-resolution, cryo-electron microscopy density map, we found that the model does not explain much of the other available experimental data. Here we propose a new model of the M2 channel derived solely from helix packing and symmetry constraints. This model agrees well with experimental results from solid-state NMR, chemical reactivity, and mutagenesis experiments. The model depicts the channel pore, the channel gate, and the residues responsible for cation specificity.
Department of Chemistry and Biochemistry and UCLA-Department of Energy Center for Genomics and Proteomics, University of California, Los Angeles, Los Angeles, California 90095, USA.
Sanguk
S
Kim
Aaron K
AK
Chamberlain
James U
JU
Bowie
D002462:Cell Membrane / Q000737:chemistry*; D003198:Computer Simulation; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry*; D008560:Membrane Fluidity; D008956:Models, Chemical; D008958:Models, Molecular; D016062:Porosity; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011978:Receptors, Nicotinic / Q000737:chemistry*; D013329:Structure-Activity Relationship
D007473:Ion Channels; D011978:Receptors, Nicotinic