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.
Roles of surface residues of intracellular domains of heag potassium channels.
Stevens L, Ju M, Wray D.
???displayArticle.abstract???
Ether-a-go-go potassium channels have large intracellular regions containing 'Per-Ant-Sim' (PAS) and cyclic nucleotide binding (cNBD) domains at the N- and C-termini, respectively. In heag1 and heag2 channels, recent studies have suggested that the N- and C-terminal domains interact, and affect activation properties. Here, we have studied the effect of mutations of residues on the surfaces of PAS and cNBD domains. For this, we introduced alanine and lysine mutations in heag1 channels, and recorded currents by two-electrode voltage clamp. In both the PAS domain and the cNBD domain, contiguous areas of conserved residues on the surfaces of these domains were found which affected the activation kinetics of the channel. Next, we investigated possible effects of mutations on domain interactions of PAS and cNBD proteins in heag2 by co-expressing these domain proteins followed by analysis with native gels and western blotting. We found oligomeric association between these domains. Mutations F30A and A609K (on the surfaces of the PAS and cNBD domains, respectively) affected oligomeric compositions of these domains when proteins for PAS and cNBD domains were expressed together. Taken together, the data suggest that the PAS and cNBD domains form interacting oligomers that have roles in channel function.
Bezanilla,
Voltage sensor movements.
2002,
Pubmed Chen,
Long QT syndrome-associated mutations in the Per-Arnt-Sim (PAS) domain of HERG potassium channels accelerate channel deactivation.
1999,
Pubmed
,
Xenbase Craven,
C-terminal movement during gating in cyclic nucleotide-modulated channels.
2008,
Pubmed
,
Xenbase Cui,
Analysis of the cyclic nucleotide binding domain of the HERG potassium channel and interactions with KCNE2.
2001,
Pubmed Gandhi,
Molecular models of voltage sensing.
2002,
Pubmed Gómez-Varela,
Influence of amino-terminal structures on kinetic transitions between several closed and open states in human erg K+ channels.
2002,
Pubmed
,
Xenbase Jiang,
The open pore conformation of potassium channels.
2002,
Pubmed Jones,
Multiple sites of interaction between the intracellular domains of an inwardly rectifying potassium channel, Kir6.2.
2001,
Pubmed Ju,
Molecular identification and characterisation of the human eag2 potassium channel.
2002,
Pubmed Ju,
Molecular regions responsible for differences in activation between heag channels.
2006,
Pubmed
,
Xenbase Ju,
The Roles of N- and C-terminal determinants in the activation of the Kv2.1 potassium channel.
2003,
Pubmed
,
Xenbase Lee,
Structure of the KvAP voltage-dependent K+ channel and its dependence on the lipid membrane.
2005,
Pubmed Lörinczi,
The voltage dependence of hEag currents is not determined solely by membrane-spanning domains.
2009,
Pubmed
,
Xenbase Milligan,
Local movement in the S2 region of the voltage-gated potassium channel hKv2.1 studied using cysteine mutagenesis.
2000,
Pubmed
,
Xenbase Mohapatra,
Interdomain cytoplasmic interactions govern the intracellular trafficking, gating, and modulation of the Kv2.1 channel.
2008,
Pubmed Morais Cabral,
Crystal structure and functional analysis of the HERG potassium channel N terminus: a eukaryotic PAS domain.
1998,
Pubmed
,
Xenbase Occhiodoro,
Cloning of a human ether-a-go-go potassium channel expressed in myoblasts at the onset of fusion.
1998,
Pubmed Pardo,
Eag1: an emerging oncological target.
2008,
Pubmed Scholle,
Effects of Kv1.2 intracellular regions on activation of Kv2.1 channels.
2004,
Pubmed
,
Xenbase Schönherr,
Molecular determinants for activation and inactivation of HERG, a human inward rectifier potassium channel.
1996,
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 Viloria,
Differential effects of amino-terminal distal and proximal domains in the regulation of human erg K(+) channel gating.
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 Wang,
Dynamic control of deactivation gating by a soluble amino-terminal domain in HERG K(+) channels.
2000,
Pubmed
,
Xenbase Yellen,
The voltage-gated potassium channels and their relatives.
2002,
Pubmed Yusaf,
Measurement of the movement of the S4 segment during the activation of a voltage-gated potassium channel.
1996,
Pubmed
,
Xenbase Zagotta,
Structural basis for modulation and agonist specificity of HCN pacemaker channels.
2003,
Pubmed
