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.
Jiang
Youxing
Y
Howard Hughes Medical Institute, Laboratory of Molecular Neurobiology and Biophysics, Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
Ruta
Vanessa
V
Chen
Jiayun
J
Lee
Alice
A
MacKinnon
Roderick
R
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