Importance of lipid-pore loop interface for potassium channel structure and function

TY - JOUR

T1 - Importance of lipid-pore loop interface for potassium channel structure and function

AU - van der Cruijsen, Elwin A W

AU - Nand, Deepak

AU - Weingarth, Markus

AU - Prokofyev, Alexander

AU - Hornig, Sönke

AU - Cukkemane, Abhishek Arun

AU - Bonvin, Alexandre M J J

AU - Becker, Stefan

AU - Hulse, Raymond E

AU - Perozo, Eduardo

AU - Pongs, Olaf

AU - Baldus, Marc

PY - 2013/8/6

Y1 - 2013/8/6

N2 - 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.

AB - 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.

KW - Amino Acid Sequence

KW - Animals

KW - Bacterial Proteins

KW - Binding Sites

KW - Female

KW - Ion Channel Gating

KW - Kv1.3 Potassium Channel

KW - Lipid Bilayers

KW - Magnetic Resonance Spectroscopy

KW - Membrane Potentials

KW - Models, Molecular

KW - Molecular Dynamics Simulation

KW - Molecular Sequence Data

KW - Mutation

KW - Oocytes

KW - Potassium Channels

KW - Protein Binding

KW - Protein Conformation

KW - Protein Structure, Tertiary

KW - Recombinant Fusion Proteins

KW - Sequence Homology, Amino Acid

KW - Xenopus

U2 - 10.1073/pnas.1305563110

DO - 10.1073/pnas.1305563110

M3 - SCORING: Journal article

C2 - 23882077

VL - 110

SP - 13008

EP - 13013

JO - P NATL ACAD SCI USA

JF - P NATL ACAD SCI USA

SN - 0027-8424

IS - 32

ER -