Coupling between voltage sensors and activation gate in voltage-gated K+ channels.
Current through voltage-gated K+ channels underlies the action potential encoding the electrical signal in excitable cells. The four subunits of a voltage-gated K+ channel each have six transmembrane segments (S1-S6), whereas some other K+ channels, such as eukaryotic inward rectifier K+ channels and the prokaryotic KcsA channel, have only two transmembrane segments (M1 and M2). A voltage-gated K+ channel is formed by an ion-pore module (S5-S6, equivalent to M1-M2) and the surrounding voltage-sensing modules. The S4 segments are the primary voltage sensors while the intracellular activation gate is located near the COOH-terminal end of S6, although the coupling mechanism between them remains unknown. In the present study, we found that two short, complementary sequences in voltage-gated K+ channels are essential for coupling the voltage sensors to the intracellular activation gate. One sequence is the so called S4-S5 linker distal to the voltage-sensing S4, while the other is around the COOH-terminal end of S6, a region containing the actual gate-forming residues.
Lu
Zhe
Z
Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104, USA. zhelu@mail.med.upenn.edu
Klem
Angela M
AM
Ramu
Yajamana
Y
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002678:Chimera; D015640:Ion Channel Gating / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology*; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D009865:Oocytes; D010086:Oxidative Phosphorylation Coupling Factors; D010446:Peptide Fragments; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry* / Q000378:metabolism*; D020836:Protein Structure, Quaternary / Q000502:physiology; D011994:Recombinant Proteins; D020539:Sequence Analysis, Protein; D051637:Shaker Superfamily of Potassium Channels; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
D008565:Membrane Proteins; D010086:Oxidative Phosphorylation Coupling Factors; D010446:Peptide Fragments; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins; C088750:S4 peptide, Drosophila Shaker potassium channel; D051637:Shaker Superfamily of Potassium Channels