Common mechanism of pore opening shared by five different potassium channels.
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 the Gaussian network model 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 corkscrew-like counterrotation of the extracellular and 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 extracellular 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.
Department of Computational Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Indira H
IH
Shrivastava
Ivet
I
Bahar
D000595:Amino Acid Sequence; D015640:Ion Channel Gating; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000737:chemistry* / Q000502:physiology; D011487:Protein Conformation
D015221:Potassium Channels