title: Structure of the voltage-gated K⁺ channel Eag1 reveals an alternative voltage sensing mechanism.
abstract: Voltage-gated potassium (K(v)) channels are gated by the movement of the transmembrane voltage sensor, which is coupled, through the helical S4-S5 linker, to the potassium pore. We determined the single-particle cryo-electron microscopy structure of mammalian K(v)10.1, or Eag1, bound to the channel inhibitor calmodulin, at 3.78 angstrom resolution. Unlike previous K(v) structures, the S4-S5 linker of Eag1 is a five-residue loop and the transmembrane segments are not domain swapped, which suggest an alternative mechanism of voltage-dependent gating. Additionally, the structure and position of the S4-S5 linker allow calmodulin to bind to the intracellular domains and to close the potassium pore, independent of voltage-sensor position. The structure reveals an alternative gating mechanism for K(v) channels and provides a template to further understand the gating properties of Eag1 and related channels.
authors: Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA.
authors: Jonathan R
authors: JR
authors: Whicher
authors: Laboratory of Molecular Neurobiology and Biophysics, The Rockefeller University, Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10065, USA. mackinn@rockefeller.edu.
authors: Roderick
authors: R
authors: MacKinnon
mesh_terms: D000818:Animals; D001665:Binding Sites; D002147:Calmodulin / Q000737:chemistry / Q000494:pharmacology; D020285:Cryoelectron Microscopy; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000648:ultrastructure; D015640:Ion Channel Gating; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats
chemical_list: D002147:Calmodulin; D051638:Ether-A-Go-Go Potassium Channels; C496886:Kcnh1 protein, rat; D026902:Potassium Channel Blockers