The principle of gating charge movement in a voltage-dependent K+ channel.
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.
Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
Youxing
Y
Jiang
Vanessa
V
Ruta
Jiayun
J
Chen
Alice
A
Lee
Roderick
R
MacKinnon
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D019843:Archaeal Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D001360:Avidin / Q000378:metabolism; D001710:Biotin / Q000378:metabolism; D019620:Desulfurococcaceae / Q000737:chemistry / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D015640:Ion Channel Gating; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009038:Motion; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D055672:Static Electricity; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D019843:Archaeal Proteins; D007140:Immunoglobulin Fab Fragments; D024642:Potassium Channels, Voltage-Gated; D001360:Avidin; D001710:Biotin