Intrinsic flexibility and gating mechanism of the potassium channel KcsA.
The gating mechanism of the potassium channel KcsA was studied by normal mode analysis. The results provided an atomic description of the locations of the pivot points and the motional features of key structural elements in the gating process. Two pivot points were found in the motions of the inner TM2 helical bundle that directly modulate the size of the central channel pore. One point is an intrasubunit hinge point that sharply divides the structural flexibility between the more rigid selectivity filter and the more mobile peripheral transmembrane helices. Such a division is vital for KcsA because it permits the large-scale motions of transmembrane helices required for the gating and, in the meantime, maintains the rigidity of the filter region essential for the selectivity. The other pivot point is an intersubunit one at which all four TM2 helices are bundled together. During the gating process, each TM2 helix undergoes a lever-like swinging motion pivoting on the intrasubunit hinge, and the entire TM2 bundle undergoes a concerted rotational motion around the central channel axis constrained around the intersubunit bundle point. This series of motions leads to a dramatic enlargement of the intracellular gate without loosening up the structural integrity.
Shen
Yufeng
Y
Graduate Program of Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, One Baylor Plaza, BCM-125, Houston, TX 77030, USA.
Kong
Yifei
Y
Ma
Jianpeng
J
D001426:Bacterial Proteins; D004578:Electron Spin Resonance Spectroscopy; D006863:Hydrogen-Ion Concentration; D007477:Ions; D008958:Models, Molecular; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012984:Software
D001426:Bacterial Proteins; D007477:Ions; D015221:Potassium Channels; C107790:prokaryotic potassium channel; D011188:Potassium