Open-state conformation of the KcsA K+ channel: Monte Carlo normal mode following simulations.
Potassium channels fluctuate between closed and open states. The detailed mechanism of the conformational changes opening the intracellular pore in the K+ channel from Streptomyces lividans (KcsA) is unknown. Applying Monte Carlo normal mode following, we find that gating involves rotation and unwinding of the TM2 bundle, lateral movement of the TM2 helices away from the channel axis, and disappearance of the TM2 bundle. The open-state conformation of KcsA exhibits a very wide inner vestibule, with a radius approximately 5-7 A and inner helices bent at the A98-G99 hinge. Computed conformational changes demonstrate that spin labeling and X-ray experiments illuminate different stages in gating: transition begins with clockwise rotation of the TM2 helices ending at a final state with the TM2 bend hinged near residues A98-G99. The concordance between the computational and experimental results provides atomic-level insights into the structural rearrangements of the channel's inner pore.
Miloshevsky
Gennady V
GV
Department of Chemistry, MS-015, Brandeis University, P.O. Box 549110, Waltham, MA 02454-9110, USA.
Jordan
Peter C
PC
D001426:Bacterial Proteins / Q000737:chemistry*; D008958:Models, Molecular; D009010:Monte Carlo Method; D015221:Potassium Channels / Q000737:chemistry*; D011487:Protein Conformation; D014961:X-Ray Diffraction
D001426:Bacterial Proteins; D015221:Potassium Channels; C107790:prokaryotic potassium channel