title: Importance of lipid-pore loop interface for potassium channel structure and function.
abstract: Potassium (i.e., K(+)) channels allow for the controlled and selective passage of potassium ions across the plasma membrane via a conserved pore domain. In voltage-gated K(+) channels, gating is the result of the coordinated action of two coupled gates: an activation gate at the intracellular entrance of the pore and an inactivation gate at the selectivity filter. By using solid-state NMR structural studies, in combination with electrophysiological experiments and molecular dynamics simulations, we show that the turret region connecting the outer transmembrane helix (transmembrane helix 1) and the pore helix behind the selectivity filter contributes to K(+) channel inactivation and exhibits a remarkable structural plasticity that correlates to K(+) channel inactivation. The transmembrane helix 1 unwinds when the K(+) channel enters the inactivated state and rewinds during the transition to the closed state. In addition to well-characterized changes at the K(+) ion coordination sites, this process is accompanied by conformational changes within the turret region and the pore helix. Further spectroscopic and computational results show that the same channel domain is critically involved in establishing functional contacts between pore domain and the cellular membrane. Taken together, our results suggest that the interaction between the K(+) channel turret region and the lipid bilayer exerts an important influence on the selective passage of potassium ions via the K(+) channel pore.
authors.affiliation: NMR Spectroscopy, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands.
authors.forename: Elwin A W
authors.initials: EA
authors.lastname: van der Cruijsen
authors.forename: Deepak
authors.initials: D
authors.lastname: Nand
authors.forename: Markus
authors.initials: M
authors.lastname: Weingarth
authors.forename: Alexander
authors.initials: A
authors.lastname: Prokofyev
authors.forename: Sönke
authors.initials: S
authors.lastname: Hornig
authors.forename: Abhishek Arun
authors.initials: AA
authors.lastname: Cukkemane
authors.forename: Alexandre M J J
authors.initials: AM
authors.lastname: Bonvin
authors.forename: Stefan
authors.initials: S
authors.lastname: Becker
authors.forename: Raymond E
authors.initials: RE
authors.lastname: Hulse
authors.forename: Eduardo
authors.initials: E
authors.lastname: Perozo
authors.forename: Olaf
authors.initials: O
authors.lastname: Pongs
authors.forename: Marc
authors.initials: M
authors.lastname: Baldus
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D005260:Female; D015640:Ion Channel Gating / Q000235:genetics / Q000502:physiology*; D051664:Kv1.3 Potassium Channel / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008564:Membrane Potentials / Q000235:genetics / Q000502:physiology; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009154:Mutation; D009865:Oocytes / Q000378:metabolism / Q000502:physiology; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014981:Xenopus
chemical_list: D001426:Bacterial Proteins; D051664:Kv1.3 Potassium Channel; D008051:Lipid Bilayers; D015221:Potassium Channels; D011993:Recombinant Fusion Proteins; C107790:prokaryotic potassium channel
keywords: ion channel; membrane protein; solid-state NMR spectroscopy