Structure Modeling of the Acetylcholine Receptor Channel and Related Ligand Gated Channels

摘要

In this model-building study a model for the pore of the acctylcholine receptor channel is proposed. The pore is formed by five n-helices of the M2 segment where three rings of hydrophilic side chains point into the channel lumen. This model is in agreement with most experimental data like photolabeling, drug affinity studies, single channel conductivity measurements and cryo electron microscopy known about this channel. This study predicts a strong coupling of the motion of the ions in the channel to that of the charged and highly hydrophitic amino acid side chains at the channel wall. Due to the negative net-charge in the pore more than a single cation may occupy the pore region. The resulting strong local electric fields make the commonly used constant field approximation obsolete for this type of ion channel.