title: Structural basis of lipid-driven conformational transitions in the KvAP voltage-sensing domain.
abstract: Voltage-gated ion channels respond to transmembrane electric fields through reorientations of the positively charged S4 helix within the voltage-sensing domain (VSD). Despite a wealth of structural and functional data, the details of this conformational change remain controversial. Recent electrophysiological evidence showed that equilibrium between the resting ('down') and activated ('up') conformations of the KvAP VSD from Aeropyrum pernix can be biased through reconstitution in lipids with or without phosphate groups. We investigated the structural transition between these functional states, using site-directed spin-labeling and EPR spectroscopic methods. Solvent accessibility and interhelical distance determinations suggest that KvAP gates through S4 movements involving an ∼3-Å upward tilt and simultaneous ∼2-Å axial shift. This motion leads to large accessibly changes in the intracellular water-filled crevice and supports a new model of gating that combines structural rearrangements and electric-field remodeling.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA.
authors.forename: Qufei
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA.
authors.forename: Sherry
authors.initials: S
authors.lastname: Wanderling
authors.affiliation: Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Pornthep
authors.initials: P
authors.lastname: Sompornpisut
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois, USA.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Perozo
mesh_terms: D041522:Aeropyrum / Q000378:metabolism*; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D008968:Molecular Conformation; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry* / Q000502:physiology; D013113:Spin Labels
chemical_list: D008055:Lipids; D024642:Potassium Channels, Voltage-Gated; D013113:Spin Labels