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Multiple interactions between cytoplasmic domains regulate slow deactivation of Kv11.1 channels.
Ng CA
,
Phan K
,
Hill AP
,
Vandenberg JI
,
Perry MD
.
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The intracellular domains of many ion channels are important for fine-tuning their gating kinetics. In Kv11.1 channels, the slow kinetics of channel deactivation, which are critical for their function in the heart, are largely regulated by the N-terminal N-Cap and Per-Arnt-Sim (PAS) domains, as well as the C-terminal cyclic nucleotide-binding homology (cNBH) domain. Here, we use mutant cycle analysis to probe for functional interactions between the N-Cap/PAS domains and the cNBH domain. We identified a specific and stable charge-charge interaction between Arg(56) of the PAS domain and Asp(803) of the cNBH domain, as well an additional interaction between the cNBH domain and the N-Cap, both of which are critical for maintaining slow deactivation kinetics. Furthermore, we found that positively charged arginine residues within the disordered region of the N-Cap interact with negatively charged residues of the C-linker domain. Although this interaction is likely more transient than the PAS-cNBD interaction, it is strong enough to stabilize the open conformation of the channel and thus slow deactivation. These findings provide novel insights into the slow deactivation mechanism of Kv11.1 channels.
Adaixo,
Structural properties of PAS domains from the KCNH potassium channels.
2013, Pubmed
Adaixo,
Structural properties of PAS domains from the KCNH potassium channels.
2013,
Pubmed
Al-Owais,
Role of intracellular domains in the function of the herg potassium channel.
2009,
Pubmed
Arnold,
The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling.
2006,
Pubmed
Barros,
Demonstration of an inwardly rectifying K+ current component modulated by thyrotropin-releasing hormone and caffeine in GH3 rat anterior pituitary cells.
1997,
Pubmed
Bauer,
RERG is a molecular correlate of the inward-rectifying K current in clonal rat pituitary cells.
1998,
Pubmed
Bordoli,
Protein structure homology modeling using SWISS-MODEL workspace.
2009,
Pubmed
Brelidze,
Structure of the carboxy-terminal region of a KCNH channel.
2012,
Pubmed
Brelidze,
Structure of the C-terminal region of an ERG channel and functional implications.
2013,
Pubmed
Chen,
Long QT syndrome-associated mutations in the Per-Arnt-Sim (PAS) domain of HERG potassium channels accelerate channel deactivation.
1999,
Pubmed
,
Xenbase
Chiesa,
A novel role for HERG K+ channels: spike-frequency adaptation.
1997,
Pubmed
Curran,
A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome.
1995,
Pubmed
Gianulis,
Direct interaction of eag domains and cyclic nucleotide-binding homology domains regulate deactivation gating in hERG channels.
2013,
Pubmed
Greenwood,
Loss of functional K+ channels encoded by ether-à-go-go-related genes in mouse myometrium prior to labour onset.
2009,
Pubmed
Guex,
SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling.
1997,
Pubmed
Gustina,
A recombinant N-terminal domain fully restores deactivation gating in N-truncated and long QT syndrome mutant hERG potassium channels.
2009,
Pubmed
,
Xenbase
Gustina,
hERG potassium channel gating is mediated by N- and C-terminal region interactions.
2011,
Pubmed
,
Xenbase
Gustina,
HERG potassium channel regulation by the N-terminal eag domain.
2012,
Pubmed
Haitin,
The structural mechanism of KCNH-channel regulation by the eag domain.
2013,
Pubmed
Lanigan,
Mutating a critical lysine in ShK toxin alters its binding configuration in the pore-vestibule region of the voltage-gated potassium channel, Kv1.3.
2002,
Pubmed
Li,
NMR solution structure of the N-terminal domain of hERG and its interaction with the S4-S5 linker.
2010,
Pubmed
Marques-Carvalho,
Structural, biochemical, and functional characterization of the cyclic nucleotide binding homology domain from the mouse EAG1 potassium channel.
2012,
Pubmed
Morais Cabral,
Crystal structure and functional analysis of the HERG potassium channel N terminus: a eukaryotic PAS domain.
1998,
Pubmed
,
Xenbase
Muskett,
Mechanistic insight into human ether-à-go-go-related gene (hERG) K+ channel deactivation gating from the solution structure of the EAG domain.
2011,
Pubmed
Ng,
The S4-S5 linker acts as a signal integrator for HERG K+ channel activation and deactivation gating.
2012,
Pubmed
Ng,
C-terminal β9-strand of the cyclic nucleotide-binding homology domain stabilizes activated states of Kv11.1 channels.
2013,
Pubmed
,
Xenbase
Ng,
The N-terminal tail of hERG contains an amphipathic α-helix that regulates channel deactivation.
2011,
Pubmed
Ohya,
Functional and molecular identification of ERG channels in murine portal vein myocytes.
2002,
Pubmed
Pardo,
Eag1 as a cancer target.
2008,
Pubmed
Piper,
Gating currents associated with intramembrane charge displacement in HERG potassium channels.
2003,
Pubmed
,
Xenbase
Sanguinetti,
A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel.
1995,
Pubmed
,
Xenbase
Schreiber,
Energetics of protein-protein interactions: analysis of the barnase-barstar interface by single mutations and double mutant cycles.
1995,
Pubmed
Schäfer,
The erg-like potassium current in rat lactotrophs.
1999,
Pubmed
Tan,
Voltage-sensing domain mode shift is coupled to the activation gate by the N-terminal tail of hERG channels.
2012,
Pubmed
,
Xenbase
Terlau,
Amino terminal-dependent gating of the potassium channel rat eag is compensated by a mutation in the S4 segment.
1997,
Pubmed
,
Xenbase
Trudeau,
HERG, a human inward rectifier in the voltage-gated potassium channel family.
1995,
Pubmed
Wang,
Dynamic control of deactivation gating by a soluble amino-terminal domain in HERG K(+) channels.
2000,
Pubmed
,
Xenbase
Wang,
Regulation of deactivation by an amino terminal domain in human ether-à-go-go-related gene potassium channels.
1998,
Pubmed
,
Xenbase
Warmke,
A family of potassium channel genes related to eag in Drosophila and mammals.
1994,
Pubmed
de la Peña,
Demonstration of physical proximity between the N terminus and the S4-S5 linker of the human ether-a-go-go-related gene (hERG) potassium channel.
2011,
Pubmed
,
Xenbase
