Abstract

A fundamental question associated with the function of ion channels is the conformational changes that allow for reversibly opening/occluding the pore through which the cations permeate. The recently elucidated crystal structures of potassium channels reveal similar structural motifs at their pore-forming regions, suggesting that they share a common gating mechanism. The validity of this hypothesis is explored by analyzing the collective dynamics of five known K+ channel structures. Normal mode analysis using Gaussian Network Model (GNM) strikingly reveals that all five structures display the same intrinsic motions at their pore-forming region despite the differences in their sequences, structures and activation mechanisms. Superposition of the most cooperative mode profiles shows that the identified common mechanism is a global cork-screw like counter-rotation of extracellular (EC) and the cytoplasmic (CP) regions, leading to the opening of the CP end of the pore. A second cooperative mode shared by all five K+ channels is the extension of the EC and/or CP ends via alternating anticorrelated fluctuations of pairs of diagonally opposite monomers. Residues acting as hinges/anchors in both modes are highly conserved across the members of the family of K+ channel proteins, consistent with their presently disclosed critical mechanical role in pore gating.

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PDB Files

Crystal Structure (shaker_0.pdb)
ANM open model (shaker_torsion_200.pdb)