ペプチドによるイオンチャネル機能の再構成 : アセチルコリン受容体ポアの構造と機能

概要

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A way of predicting the high-order structure of channel proteins from the primary structure was reviewed by taking the acetylcholine receptor (AChR) as an example. The Finer-Moore & Stroud plot was applied to designate an amphipathic secondary structure among possible candidates. The site-directed mutagenesis elucidated the amino acids accessible for permeating ions or blockers. For construction of the pore structure we utilized the low-resolution quarternary structure with pseudoradial. symmetry obtained by electron micrograph as constraint. To test this model, a pore was functionally reconstituted with segments dissected from the primary structure of Torpedo AChR. Synthetic 23-mer peptides that mimic the M2 and M1 transmembrane segments of AChR were incorporated into planar lipid bilayers. The peptide corresponding to M2, but not to Ml, exhibited channel activity with bursting, behavior. The conductance ratio among monovalent cations as well as the open channel time was similar to those of the authentic AChR. A model for the peptide pore was assembled by computer simulation under symmetrical conditions. An energy optimized homopentamer fulfilled the cut-off size of the pore. The conjectured heteropentamer for the authentic channel and the simulated homopentemer for the peptide pore were compared.