Streptomyces lividans (actinobacteria)
Potassium channel is a membrane protein which selectively permeates potassium ion across the membrane and regulates the membrane potential. In 1998, MacKinnon and his colleagues reported the crystal structure of a prokaryotic two transmembrane potassium channel KcsA, and revealed the mechanism of the potassium selectivity and the tremendous amount of permeability (10^6 potassium ions/sec). By these great works, MacKinnon won the Nobel prize of chemistry in 2003. MacKinnon and his colleagues nicely revealed the permeation mechanism of potassium channel. Together with the permeation mechanism, the gating mechanism of ion channels is very important. According to the condition around the plasma membrane such as pH, membrane voltage, the gate of the ion channels transits two states, open and close. Especially, KcsA is rapidly inactivated by proton after the transient activation. This inactivation is considered to be related to the voltage dependent inactivation of voltage dependent potassium channels.
Perozo et al. showed E71, which is in the selectivity filter of KcsA, is an important amino acid in the inactivation. In the crystal structure of E71A mutant, D81 is flipped to the pore because of the loss of hydrogen bond network among W67, E71 and D81. Furthermore, proton activates but does not inactivate this mutant. These results implied that structural change caused by the interaction between W67, E71 and D81 induces the proton dependent inactivation process.
Protein Data Bank (PDB)
Cordero-Morales, J.F. Cuello, L.G. Zhao, Y. Jogini, V. Cortes, D.M. Roux, B. Perozo, E.; "Molecular determinants of gating at the potassium-channel selectivity filter."; Nat.Struct.Mol.Biol.; (2006) 13:311-318 PubMed:16532009.
author: Daisuke Ino