Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Biophys J
2010 Dec 01;9911:3599-608. doi: 10.1016/j.bpj.2010.10.018.
Show Gene links
Show Anatomy links
KCNE1 remodels the voltage sensor of Kv7.1 to modulate channel function.
Wu D
,
Pan H
,
Delaloye K
,
Cui J
.
???displayArticle.abstract???
The KCNE1 auxiliary subunit coassembles with the Kv7.1 channel and modulates its properties to generate the cardiac I(Ks) current. Recent biophysical evidence suggests that KCNE1 interacts with the voltage-sensing domain (VSD) of Kv7.1. To investigate the mechanism of how KCNE1 affects the VSD to alter the voltage dependence of channel activation, we perturbed the VSD of Kv7.1 by mutagenesis and chemical modification in the absence and presence of KCNE1. Mutagenesis of S4 in Kv7.1 indicates that basic residues in the N-terminal half (S4-N) and C-terminal half (S4-C) of S4 are important for stabilizing the resting and activated states of the channel, respectively. KCNE1 disrupts electrostatic interactions involving S4-C, specifically with the lower conserved glutamate in S2 (Glu(170) or E2). Likewise, Trp scanning of S4 shows that mutations to a cluster of residues in S4-C eliminate current in the presence of KCNE1. In addition, KCNE1 affects S4-N by enhancing MTS accessibility to the top of the VSD. Consistent with the structure of Kv channels and previous studies on the KCNE1-Kv7.1 interaction, these results suggest that KCNE1 alters the interactions of S4 residues with the surrounding protein environment, possibly by changing the protein packing around S4, thereby affecting the voltage dependence of Kv7.1.
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
Bao,
Gating and ionic currents reveal how the BKCa channel's Ca2+ sensitivity is enhanced by its beta1 subunit.
2005,
Pubmed
,
Xenbase
Barhanin,
K(V)LQT1 and lsK (minK) proteins associate to form the I(Ks) cardiac potassium current.
1996,
Pubmed
,
Xenbase
Börjesson,
Structure, function, and modification of the voltage sensor in voltage-gated ion channels.
2008,
Pubmed
Chen,
Functional interactions between KCNE1 C-terminus and the KCNQ1 channel.
2009,
Pubmed
Chen,
KCNQ1 gain-of-function mutation in familial atrial fibrillation.
2003,
Pubmed
Chen,
Pore- and state-dependent cadmium block of I(Ks) channels formed with MinK-55C and wild-type KCNQ1 subunits.
2003,
Pubmed
,
Xenbase
Choi,
A shared mechanism for lipid- and beta-subunit-coordinated stabilization of the activated K+ channel voltage sensor.
2010,
Pubmed
,
Xenbase
Chouabe,
Novel mutations in KvLQT1 that affect Iks activation through interactions with Isk.
2000,
Pubmed
Chung,
Location of KCNE1 relative to KCNQ1 in the I(KS) potassium channel by disulfide cross-linking of substituted cysteines.
2009,
Pubmed
DeCaen,
Sequential formation of ion pairs during activation of a sodium channel voltage sensor.
2009,
Pubmed
Dougherty,
The dipeptidyl-aminopeptidase-like protein 6 is an integral voltage sensor-interacting beta-subunit of neuronal K(V)4.2 channels.
2009,
Pubmed
Elinder,
S4 charges move close to residues in the pore domain during activation in a K channel.
2001,
Pubmed
,
Xenbase
Franqueza,
Long QT syndrome-associated mutations in the S4-S5 linker of KvLQT1 potassium channels modify gating and interaction with minK subunits.
1999,
Pubmed
,
Xenbase
Haitin,
Intracellular domains interactions and gated motions of I(KS) potassium channel subunits.
2009,
Pubmed
,
Xenbase
Hong,
The lipid-protein interface of a Shaker K(+) channel.
2000,
Pubmed
,
Xenbase
Jespersen,
The KCNQ1 potassium channel: from gene to physiological function.
2005,
Pubmed
Kang,
Structure of KCNE1 and implications for how it modulates the KCNQ1 potassium channel.
2008,
Pubmed
Keating,
Molecular and cellular mechanisms of cardiac arrhythmias.
2001,
Pubmed
Kurokawa,
TEA(+)-sensitive KCNQ1 constructs reveal pore-independent access to KCNE1 in assembled I(Ks) channels.
2001,
Pubmed
Liu,
Locations of the beta1 transmembrane helices in the BK potassium channel.
2008,
Pubmed
Liu,
Location of modulatory beta subunits in BK potassium channels.
2010,
Pubmed
Long,
Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment.
2007,
Pubmed
Long,
Voltage sensor of Kv1.2: structural basis of electromechanical coupling.
2005,
Pubmed
Long,
Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
2005,
Pubmed
Lvov,
Identification of a protein-protein interaction between KCNE1 and the activation gate machinery of KCNQ1.
2010,
Pubmed
Melman,
KCNE1 binds to the KCNQ1 pore to regulate potassium channel activity.
2004,
Pubmed
Monks,
Helical structure and packing orientation of the S2 segment in the Shaker K+ channel.
1999,
Pubmed
,
Xenbase
Morrow,
Defining the BK channel domains required for beta1-subunit modulation.
2006,
Pubmed
Nakajo,
KCNE1 and KCNE3 stabilize and/or slow voltage sensing S4 segment of KCNQ1 channel.
2007,
Pubmed
,
Xenbase
Nerbonne,
Molecular physiology of cardiac repolarization.
2005,
Pubmed
Orio,
Differential effects of beta 1 and beta 2 subunits on BK channel activity.
2005,
Pubmed
,
Xenbase
Panaghie,
The role of S4 charges in voltage-dependent and voltage-independent KCNQ1 potassium channel complexes.
2007,
Pubmed
,
Xenbase
Papazian,
Electrostatic interactions of S4 voltage sensor in Shaker K+ channel.
1995,
Pubmed
,
Xenbase
Park,
Impaired KCNQ1-KCNE1 and phosphatidylinositol-4,5-bisphosphate interaction underlies the long QT syndrome.
2005,
Pubmed
Pongs,
Ancillary subunits associated with voltage-dependent K+ channels.
2010,
Pubmed
Restier,
Mechanisms by which atrial fibrillation-associated mutations in the S1 domain of KCNQ1 slow deactivation of IKs channels.
2008,
Pubmed
,
Xenbase
Rocheleau,
KCNE peptides differently affect voltage sensor equilibrium and equilibration rates in KCNQ1 K+ channels.
2008,
Pubmed
,
Xenbase
Sanguinetti,
Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel.
1996,
Pubmed
,
Xenbase
Savalli,
Modes of operation of the BKCa channel beta2 subunit.
2007,
Pubmed
,
Xenbase
Seoh,
Voltage-sensing residues in the S2 and S4 segments of the Shaker K+ channel.
1996,
Pubmed
,
Xenbase
Shamgar,
KCNE1 constrains the voltage sensor of Kv7.1 K+ channels.
2008,
Pubmed
,
Xenbase
Sigg,
A physical model of potassium channel activation: from energy landscape to gating kinetics.
2003,
Pubmed
,
Xenbase
Silva,
A multiscale model linking ion-channel molecular dynamics and electrostatics to the cardiac action potential.
2009,
Pubmed
Smith-Maxwell,
Uncharged S4 residues and cooperativity in voltage-dependent potassium channel activation.
1998,
Pubmed
,
Xenbase
Soler-Llavina,
Functional interactions at the interface between voltage-sensing and pore domains in the Shaker K(v) channel.
2006,
Pubmed
,
Xenbase
Splawski,
Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2.
2000,
Pubmed
Tai,
The conduction pore of a cardiac potassium channel.
1998,
Pubmed
,
Xenbase
Tapper,
MinK subdomains that mediate modulation of and association with KvLQT1.
2000,
Pubmed
,
Xenbase
Tapper,
Location and orientation of minK within the I(Ks) potassium channel complex.
2001,
Pubmed
,
Xenbase
Tiwari-Woodruff,
Electrostatic interactions between transmembrane segments mediate folding of Shaker K+ channel subunits.
1997,
Pubmed
,
Xenbase
Tombola,
How does voltage open an ion channel?
2006,
Pubmed
Wu,
State-dependent electrostatic interactions of S4 arginines with E1 in S2 during Kv7.1 activation.
2010,
Pubmed
,
Xenbase
Xu,
KCNQ1 and KCNE1 in the IKs channel complex make state-dependent contacts in their extracellular domains.
2008,
Pubmed
,
Xenbase
Yang,
Subunit-specific effect of the voltage sensor domain on Ca2+ sensitivity of BK channels.
2008,
Pubmed
,
Xenbase
Yang,
Molecular basis of charge movement in voltage-gated sodium channels.
1996,
Pubmed
Zhang,
Contribution of hydrophobic and electrostatic interactions to the membrane integration of the Shaker K+ channel voltage sensor domain.
2007,
Pubmed
Zheng,
Analysis of the interactions between the C-terminal cytoplasmic domains of KCNQ1 and KCNE1 channel subunits.
2010,
Pubmed
