(Journal Article): The principle of gating charge movement in a voltage-dependent K+ channel.
Jiang Y, Ruta V, Chen J, Lee A, MacKinnon R (Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA)
IN:
Nature
2003; 423(6935):42-48
Impact Factor(s) of Nature: 29.273 (2005), 32.182 (2004), 30.979 (2003), 30.432 (2002), 27.955 (2001)
ABSTRACT: The steep dependence of channel opening on membrane voltage allows voltage-dependent K+ channels to turn on almost like a switch. Opening is driven by the movement of gating charges that originate from arginine residues on helical S4 segments of the protein. Each S4 segment forms half of a 'voltage-sensor paddle' on the channel's outer perimeter. Here we show that the voltage-sensor paddles are positioned inside the membrane, near the intracellular surface, when the channel is closed, and that the paddles move a large distance across the membrane from inside to outside when the channel opens. KvAP channels were reconstituted into planar lipid membranes and studied using monoclonal Fab fragments, a voltage-sensor toxin, and avidin binding to tethered biotin. Our findings lead us to conclude that the voltage-sensor paddles operate somewhat like hydrophobic cations attached to levers, enabling the membrane electric field to open and close the pore.
TYPE OF PUBLICATION: Original article
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