Antoine Taly - Normal mode analysis suggests a quaternary twist model for the nicotinic receptor gating mechanism.

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      Publication Details (including relevant citation   information):

      Biophys J. 2005 Jun;88(6):3954-65.


      We present a three-dimensional model of the homopentameric alpha7   nicotinic acetylcholine receptor (nAChR), that includes the   extracellular and membrane domains, developed by comparative   modeling on the basis of: 1), the x-ray crystal structure of the   snail acetylcholine binding protein, an homolog of the   extracellular domain of nAChRs; and 2), cryo-electron microscopy   data of the membrane domain collected on Torpedo marmorata   nAChRs. We performed normal mode analysis on the complete   three-dimensional model to explore protein flexibility. Among the   first 10 lowest frequency modes, only the first mode produces a   structural reorganization compatible with channel gating: a wide   opening of the channel pore caused by a concerted symmetrical   quaternary twist motion of the protein with opposing rotations of   the upper (extracellular) and lower (transmembrane) domains.   Still, significant reorganizations are observed within each   subunit, that involve their bending at the domain interface, an   increase of angle between the two beta-sheets composing the   extracellular domain, the internal beta-sheet being significantly   correlated to the movement of the M2 alpha-helical segment. This   global symmetrical twist motion of the pentameric protein   complex, which resembles the opening transition of other   multimeric ion channels, reasonably accounts for the available   experimental data and thus likely describes the nAChR gating   process.

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