Three-dimensional structure of I(to); Kv4.2-KChIP2 ion channels by electron microscopy at 21 Angstrom resolution.
Regulatory KChIP2 subunits assemble with pore-forming Kv4.2 subunits in 4:4 complexes to produce native voltage-gated potassium (Kv) channels like cardiac I(to) and neuronal I(A) subtypes. Here, negative stain electron microscopy (EM) and single particle averaging reveal KChIP2 to create a novel approximately 35 x 115 x 115 Angstrom, intracellular fenestrated rotunda: four peripheral columns that extend down from the membrane-embedded portion of the channel to enclose the Kv4.2 "hanging gondola" (a platform held beneath the transmembrane conduction pore by four internal columns). To reach the pore from the cytosol, ions traverse one of four external fenestrae to enter the rotundal vestibule and then cross one of four internal windows in the gondola.
Department of Pediatrics, Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06535, USA.
Leo A
LA
Kim
Johannes
J
Furst
David
D
Gutierrez
Margaret H
MH
Butler
Shuhua
S
Xu
Steve A N
SA
Goldstein
Nikolaus
N
Grigorieff
D000818:Animals; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D051605:Kv Channel-Interacting Proteins; D008564:Membrane Potentials / Q000502:physiology; D008854:Microscopy, Electron; D015394:Molecular Structure; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D024642:Potassium Channels, Voltage-Gated; D017434:Protein Structure, Tertiary / Q000502:physiology; D051672:Shal Potassium Channels
D002135:Calcium-Binding Proteins; C497018:KCND2 protein, human; C496752:KCNIP2 protein, human; D051605:Kv Channel-Interacting Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051672:Shal Potassium Channels