Structural organization of the voltage sensor in voltage-dependent potassium channels.
The structural organization of the voltage sensor in K+ channels has been investigated by second site suppressor analysis in Shaker and by identification of a metal ion binding site in ether-à-go-go (eag). In Shaker, two groups of interacting charged residues have been identified. K374 in the S4 segment interacts with E293 in S2 and D316 in S3, whereas E283 in S2 interacts with R368 and R371, two voltage-sensing residues in S4. Interactions of E283 with R368 and R371 are voltage dependent. The results suggest that E283 is located in a water-filled pocket near the extracellular surface of the protein. During voltage-dependent activation of Shaker channels, R368 and R371 move into this pocket and come into proximity with E283. In eag channels, extracellular Mg2+ directly modulates the activation process by binding to two acidic residues that are located in an analogous pocket. These acidic residues are found only in eag family members, accounting for the specificity of Mg2+ modulation to that family. These compatible results from Shaker and eag suggest a model for the packing and conformational changes of transmembrane segments in the voltage sensor of K+ channels.
Papazian
Diane M
DM
Department of Physiology, UCLA School of Medicine, Los Angeles, CA 90095-1751, USA.
Silverman
William R
WR
Lin
Meng-Chin A
MC
Tiwari-Woodruff
Seema K
SK
Tang
Chih-Yung
CY
D000595:Amino Acid Sequence; D000818:Animals; D015640:Ion Channel Gating / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D015221:Potassium Channels / Q000737:chemistry / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry* / Q000502:physiology*; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D051637:Shaker Superfamily of Potassium Channels
D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins; D051637:Shaker Superfamily of Potassium Channels