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The pore helix dipole has a minor role in inward rectifier channel function.
Chatelain FC, Alagem N, Xu Q, Pancaroglu R, Reuveny E, Minor DL.
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Ion channels lower the energetic barrier for ion passage across cell membranes and enable the generation of bioelectricity. Electrostatic interactions between permeant ions and channel pore helix dipoles have been proposed as a general mechanism for facilitating ion passage. Here, using genetic selections to probe interactions of an exemplar potassium channel blocker, barium, with the inward rectifier Kir2.1, we identify mutants bearing positively charged residues in the potassium channel signature sequence at the pore helix C terminus. We show that these channels are functional, selective, resistant to barium block, and have minimally altered conductance properties. Both the experimental data and model calculations indicate that barium resistance originates from electrostatics. We demonstrate that potassium channel function is remarkably unperturbed when positive charges occur near the permeant ions at a location that should counteract pore helix electrostatic effects. Thus, contrary to accepted models, the pore helix dipole seems to be a minor factor in potassium channel permeation.
Alagem,
Mechanism of Ba(2+) block of a mouse inwardly rectifying K+ channel: differential contribution by two discrete residues.
2001, Pubmed,
Xenbase
Alagem,
Mechanism of Ba(2+) block of a mouse inwardly rectifying K+ channel: differential contribution by two discrete residues.
2001,
Pubmed
,
Xenbase Allen,
On the importance of atomic fluctuations, protein flexibility, and solvent in ion permeation.
2004,
Pubmed Aqvist,
Ion permeation mechanism of the potassium channel.
2000,
Pubmed Aqvist,
Dipoles localized at helix termini of proteins stabilize charges.
1991,
Pubmed Armstrong,
Interaction of barium ions with potassium channels in squid giant axons.
1980,
Pubmed Bernèche,
Energetics of ion conduction through the K+ channel.
2001,
Pubmed Bernèche,
A microscopic view of ion conduction through the K+ channel.
2003,
Pubmed Bichet,
Merging functional studies with structures of inward-rectifier K(+) channels.
2003,
Pubmed Bichet,
Evolving potassium channels by means of yeast selection reveals structural elements important for selectivity.
2004,
Pubmed
,
Xenbase Doyle,
The structure of the potassium channel: molecular basis of K+ conduction and selectivity.
1998,
Pubmed Dutzler,
X-ray structure of a ClC chloride channel at 3.0 A reveals the molecular basis of anion selectivity.
2002,
Pubmed Faraldo-Gómez,
Electrostatics of ion stabilization in a ClC chloride channel homologue from Escherichia coli.
2004,
Pubmed Gaber,
TRK1 encodes a plasma membrane protein required for high-affinity potassium transport in Saccharomyces cerevisiae.
1988,
Pubmed Hamill,
Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.
1981,
Pubmed Heginbotham,
Mutations in the K+ channel signature sequence.
1994,
Pubmed
,
Xenbase Jan,
Cloned potassium channels from eukaryotes and prokaryotes.
1997,
Pubmed Jiang,
X-ray structure of a voltage-dependent K+ channel.
2003,
Pubmed Jiang,
The barium site in a potassium channel by x-ray crystallography.
2000,
Pubmed Jiang,
Crystal structure and mechanism of a calcium-gated potassium channel.
2002,
Pubmed Kubo,
Probing pore topology and conformational changes of Kir2.1 potassium channels by cysteine scanning mutagenesis.
1998,
Pubmed Kubo,
Primary structure and functional expression of a mouse inward rectifier potassium channel.
1993,
Pubmed
,
Xenbase Kuo,
Crystal structure of the potassium channel KirBac1.1 in the closed state.
2003,
Pubmed Lockhart,
Internal stark effect measurement of the electric field at the amino terminus of an alpha helix.
1992,
Pubmed Lu,
Mechanism of rectification in inward-rectifier K+ channels.
2004,
Pubmed MacKinnon,
Potassium channels and the atomic basis of selective ion conduction (Nobel Lecture).
2004,
Pubmed Minor,
Transmembrane structure of an inwardly rectifying potassium channel.
1999,
Pubmed Miranda,
Position-dependent interactions between cysteine residues and the helix dipole.
2003,
Pubmed Morais-Cabral,
Energetic optimization of ion conduction rate by the K+ selectivity filter.
2001,
Pubmed Nakamura,
Roles of electrostatic interaction in proteins.
1996,
Pubmed Neyton,
Potassium blocks barium permeation through a calcium-activated potassium channel.
1988,
Pubmed Neyton,
Discrete Ba2+ block as a probe of ion occupancy and pore structure in the high-conductance Ca2+ -activated K+ channel.
1988,
Pubmed Noskov,
Control of ion selectivity in potassium channels by electrostatic and dynamic properties of carbonyl ligands.
2004,
Pubmed Numann,
High-throughput screening strategies for cardiac ion channels.
2001,
Pubmed Parsegian,
Energy of an ion crossing a low dielectric membrane: solutions to four relevant electrostatic problems.
1969,
Pubmed Proks,
The ligand-sensitive gate of a potassium channel lies close to the selectivity filter.
2003,
Pubmed
,
Xenbase Reuveny,
Contributions of a negatively charged residue in the hydrophobic domain of the IRK1 inwardly rectifying K+ channel to K(+)-selective permeation.
1996,
Pubmed
,
Xenbase Rocchia,
Rapid grid-based construction of the molecular surface and the use of induced surface charge to calculate reaction field energies: applications to the molecular systems and geometric objects.
2002,
Pubmed Roux,
The cavity and pore helices in the KcsA K+ channel: electrostatic stabilization of monovalent cations.
1999,
Pubmed Roux,
The art of dissecting the function of a potassium channel.
2005,
Pubmed Sadja,
Coupling Gbetagamma-dependent activation to channel opening via pore elements in inwardly rectifying potassium channels.
2001,
Pubmed
,
Xenbase Schwede,
SWISS-MODEL: An automated protein homology-modeling server.
2003,
Pubmed Sitkoff,
Calculation of electrostatic effects at the amino terminus of an alpha helix.
1994,
Pubmed Vergara,
Localization of the K+ lock-In and the Ba2+ binding sites in a voltage-gated calcium-modulated channel. Implications for survival of K+ permeability.
1999,
Pubmed Woodhull,
Ionic blockage of sodium channels in nerve.
1973,
Pubmed Word,
Asparagine and glutamine: using hydrogen atom contacts in the choice of side-chain amide orientation.
1999,
Pubmed Yi,
Yeast screen for constitutively active mutant G protein-activated potassium channels.
2001,
Pubmed
,
Xenbase Zaks-Makhina,
Novel neuroprotective K+ channel inhibitor identified by high-throughput screening in yeast.
2004,
Pubmed Zhou,
Mutations in the pore region of ROMK enhance Ba2+ block.
1996,
Pubmed
,
Xenbase Zhou,
A mutant KcsA K(+) channel with altered conduction properties and selectivity filter ion distribution.
2004,
Pubmed Zhou,
Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 A resolution.
2001,
Pubmed
