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Divalent cations slow activation of EAG family K+ channels through direct binding to S4.
Zhang X
,
Bursulaya B
,
Lee CC
,
Chen B
,
Pivaroff K
,
Jegla T
.
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Voltage-gated K+ channels share a common voltage sensor domain (VSD) consisting of four transmembrane helices, including a highly mobile S4 helix that contains the major gating charges. Activation of ether-a-go-go (EAG) family K+ channels is sensitive to external divalent cations. We show here that divalent cations slow the activation rate of two EAG family channels (Kv12.1 and Kv10.2) by forming a bridge between a residue in the S4 helix and acidic residues in S2. Histidine 328 in the S4 of Kv12.1 favors binding of Zn2+ and Cd2+, whereas the homologous residue Serine 321 in Kv10.2 contributes to effects of Mg2+ and Ni2+. This novel finding provides structural constraints for the position of transmembrane VSD helices in closed, ion-bound EAG family channels. Homology models of Kv12.1 and Kv10.2 VSD structures based on a closed-state model of the Shaker family K+ channel Kv1.2 match these constraints. Our results suggest close conformational conservation between closed EAG and Shaker family channels, despite large differences in voltage sensitivity, activation rates, and activation thresholds.
Aggarwal,
Contribution of the S4 segment to gating charge in the Shaker K+ channel.
1996, Pubmed,
Xenbase
Aggarwal,
Contribution of the S4 segment to gating charge in the Shaker K+ channel.
1996,
Pubmed
,
Xenbase
Ahern,
Focused electric field across the voltage sensor of potassium channels.
2005,
Pubmed
,
Xenbase
Baker,
Three transmembrane conformations and sequence-dependent displacement of the S4 domain in shaker K+ channel gating.
1998,
Pubmed
Bannister,
Optical detection of rate-determining ion-modulated conformational changes of the ether-à-go-go K+ channel voltage sensor.
2005,
Pubmed
,
Xenbase
Campos,
Two atomic constraints unambiguously position the S4 segment relative to S1 and S2 segments in the closed state of Shaker K channel.
2007,
Pubmed
,
Xenbase
Engeland,
Cloning and functional expression of rat ether-à-go-go-like K+ channel genes.
1998,
Pubmed
Fernandez,
Molecular mapping of a site for Cd2+-induced modification of human ether-à-go-go-related gene (hERG) channel activation.
2005,
Pubmed
,
Xenbase
Islas,
Voltage sensitivity and gating charge in Shaker and Shab family potassium channels.
1999,
Pubmed
,
Xenbase
Jegla,
A novel subunit for shal K+ channels radically alters activation and inactivation.
1997,
Pubmed
Jegla,
Evolution of the human ion channel set.
2009,
Pubmed
Ledwell,
Mutations in the S4 region isolate the final voltage-dependent cooperative step in potassium channel activation.
1999,
Pubmed
,
Xenbase
Lee,
Structure of the KvAP voltage-dependent K+ channel and its dependence on the lipid membrane.
2005,
Pubmed
Long,
Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
2005,
Pubmed
Long,
Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment.
2007,
Pubmed
Ludwig,
Functional expression of a rat homologue of the voltage gated either á go-go potassium channel reveals differences in selectivity and activation kinetics between the Drosophila channel and its mammalian counterpart.
1994,
Pubmed
,
Xenbase
Ma,
An extracellular Cu2+ binding site in the voltage sensor of BK and Shaker potassium channels.
2008,
Pubmed
,
Xenbase
Papazian,
Electrostatic interactions of S4 voltage sensor in Shaker K+ channel.
1995,
Pubmed
,
Xenbase
Pathak,
The cooperative voltage sensor motion that gates a potassium channel.
2005,
Pubmed
,
Xenbase
Pathak,
Closing in on the resting state of the Shaker K(+) channel.
2007,
Pubmed
Phillips,
Scalable molecular dynamics with NAMD.
2005,
Pubmed
Qian,
Visualization of transmitter release with zinc fluorescence detection at the mouse hippocampal mossy fibre synapse.
2005,
Pubmed
Rulísek,
Coordination geometries of selected transition metal ions (Co2+, Ni2+, Cu2+, Zn2+, Cd2+, and Hg2+) in metalloproteins.
1998,
Pubmed
Sands,
How does a voltage sensor interact with a lipid bilayer? Simulations of a potassium channel domain.
2007,
Pubmed
Schönherr,
Individual subunits contribute independently to slow gating of bovine EAG potassium channels.
1999,
Pubmed
Schönherr,
Conformational switch between slow and fast gating modes: allosteric regulation of voltage sensor mobility in the EAG K+ channel.
2002,
Pubmed
,
Xenbase
Seebeck,
Modeling of metal interaction geometries for protein-ligand docking.
2008,
Pubmed
Seoh,
Voltage-sensing residues in the S2 and S4 segments of the Shaker K+ channel.
1996,
Pubmed
,
Xenbase
Silverman,
Mg(2+) modulates voltage-dependent activation in ether-à-go-go potassium channels by binding between transmembrane segments S2 and S3.
2000,
Pubmed
,
Xenbase
Silverman,
Structural basis of two-stage voltage-dependent activation in K+ channels.
2003,
Pubmed
,
Xenbase
Silverman,
Binding site in eag voltage sensor accommodates a variety of ions and is accessible in closed channel.
2004,
Pubmed
,
Xenbase
Starace,
A proton pore in a potassium channel voltage sensor reveals a focused electric field.
2004,
Pubmed
Tang,
Extracellular Mg(2+) modulates slow gating transitions and the opening of Drosophila ether-à-Go-Go potassium channels.
2000,
Pubmed
,
Xenbase
Terlau,
Extracellular Mg2+ regulates activation of rat eag potassium channel.
1996,
Pubmed
,
Xenbase
Tombola,
Voltage-sensing arginines in a potassium channel permeate and occlude cation-selective pores.
2005,
Pubmed
,
Xenbase
Tombola,
The twisted ion-permeation pathway of a resting voltage-sensing domain.
2007,
Pubmed
,
Xenbase
Treptow,
Environment of the gating charges in the Kv1.2 Shaker potassium channel.
2006,
Pubmed
Trudeau,
Functional analysis of a mouse brain Elk-type K+ channel.
1999,
Pubmed
,
Xenbase
Zagotta,
Shaker potassium channel gating. III: Evaluation of kinetic models for activation.
1994,
Pubmed
,
Xenbase
Zou,
Distribution and functional properties of human KCNH8 (Elk1) potassium channels.
2003,
Pubmed
,
Xenbase
