Common Mechanism of Pore Opening Shared by Five Different Potassium Channels

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• 作者：Indira H. Shrivastava ; Ivet Bahar
• 刊名：Biophysical Journal
• 出版年：2006
• 出版时间：1 June 2006
• 年：2006
• 卷：90
• 期：11
• 页码：3929-3940
• 全文大小：1178 K

文摘

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.