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.
Proc Natl Acad Sci U S A
2014 May 27;11121:7855-60. doi: 10.1073/pnas.1401917111.
Show Gene links
Show Anatomy links
Family of prokaryote cyclic nucleotide-modulated ion channels.
Brams M
,
Kusch J
,
Spurny R
,
Benndorf K
,
Ulens C
.
???displayArticle.abstract???
Cyclic nucleotide-modulated ion channels are molecular pores that mediate the passage of ions across the cell membrane in response to cAMP or GMP. Structural insight into this class of ion channels currently comes from a related homolog, MloK1, that contains six transmembrane domains and a cytoplasmic cyclic nucleotide binding domain. However, unlike eukaryote hyperpolarization-activated cyclic nucleotide-modulated (HCN) and cyclic nucleotide-gated (CNG) channels, MloK1 lacks a C-linker region, which critically contributes to the molecular coupling between ligand binding and channel opening. In this study, we report the identification and characterization of five previously unidentified prokaryote homologs with high sequence similarity (24-32%) to eukaryote HCN and CNG channels and that contain a C-linker region. Biochemical characterization shows that two homologs, termed AmaK and SthK, can be expressed and purified as detergent-solubilized protein from Escherichia coli membranes. Expression of SthK channels in Xenopus laevis oocytes and functional characterization using the patch-clamp technique revealed that the channels are gated by cAMP, but not cGMP, are highly selective for K(+) ions over Na(+) ions, generate a large unitary conductance, and are only weakly voltage dependent. These properties resemble essential properties of various eukaryote HCN or CNG channels. Our results contribute to an understanding of the evolutionary origin of cyclic nucleotide-modulated ion channels and pave the way for future structural and functional studies.
Altieri,
Structural and energetic analysis of activation by a cyclic nucleotide binding domain.
2008, Pubmed
Altieri,
Structural and energetic analysis of activation by a cyclic nucleotide binding domain.
2008,
Pubmed
Altschul,
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
1997,
Pubmed
Angelov,
Genome sequence of the polysaccharide-degrading, thermophilic anaerobe Spirochaeta thermophila DSM 6192.
2010,
Pubmed
Anselmi,
Origin of functional diversity among tetrameric voltage-gated channels.
2007,
Pubmed
Baruscotti,
Pacemaker channels.
2004,
Pubmed
Biel,
Hyperpolarization-activated cation channels: from genes to function.
2009,
Pubmed
Biel,
Cyclic nucleotide-gated cation channels molecular diversity, structure, and cellular functions.
1996,
Pubmed
Bocquet,
A prokaryotic proton-gated ion channel from the nicotinic acetylcholine receptor family.
2007,
Pubmed
,
Xenbase
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
Chan,
Bimodal agonism in heteromeric cyclic nucleotide-gated channels.
2009,
Pubmed
Chen,
Properties of hyperpolarization-activated pacemaker current defined by coassembly of HCN1 and HCN2 subunits and basal modulation by cyclic nucleotide.
2001,
Pubmed
,
Xenbase
Choi,
Identification and characterization of a novel bacterial ATP-sensitive K+ channel.
2010,
Pubmed
,
Xenbase
Clayton,
Structure of the transmembrane regions of a bacterial cyclic nucleotide-regulated channel.
2008,
Pubmed
Clayton,
Structural basis of ligand activation in a cyclic nucleotide regulated potassium channel.
2004,
Pubmed
Cortes,
Structural dynamics of the Streptomyces lividans K+ channel (SKC1): oligomeric stoichiometry and stability.
1997,
Pubmed
,
Xenbase
Craven,
CNG and HCN channels: two peas, one pod.
2006,
Pubmed
Dekker,
Cooperative gating between single HCN pacemaker channels.
2006,
Pubmed
Derebe,
Structural studies of ion permeation and Ca2+ blockage of a bacterial channel mimicking the cyclic nucleotide-gated channel pore.
2011,
Pubmed
DiFrancesco,
Characterization of single pacemaker channels in cardiac sino-atrial node cells.
,
Pubmed
Drew,
Optimization of membrane protein overexpression and purification using GFP fusions.
2006,
Pubmed
Flynn,
Structure and rearrangements in the carboxy-terminal region of SpIH channels.
2007,
Pubmed
,
Xenbase
Frings,
Properties of cyclic nucleotide-gated channels mediating olfactory transduction. Activation, selectivity, and blockage.
1992,
Pubmed
Kaupp,
Primary structure and functional expression from complementary DNA of the rod photoreceptor cyclic GMP-gated channel.
1989,
Pubmed
,
Xenbase
Kaupp,
Cyclic nucleotide-gated ion channels.
2002,
Pubmed
Kawate,
Fluorescence-detection size-exclusion chromatography for precrystallization screening of integral membrane proteins.
2006,
Pubmed
Kuo,
Prokaryotic K(+) channels: from crystal structures to diversity.
2005,
Pubmed
Kuo,
Patch clamp and phenotypic analyses of a prokaryotic cyclic nucleotide-gated K+ channel using Escherichia coli as a host.
2007,
Pubmed
Kusch,
Effects of permeating ions and cGMP on gating and conductance of rod-type cyclic nucleotide-gated (CNGA1) channels.
2004,
Pubmed
,
Xenbase
Larkin,
Clustal W and Clustal X version 2.0.
2007,
Pubmed
Lolicato,
Tetramerization dynamics of C-terminal domain underlies isoform-specific cAMP gating in hyperpolarization-activated cyclic nucleotide-gated channels.
2011,
Pubmed
,
Xenbase
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
Maksaev,
Expression and characterization of the bacterial mechanosensitive channel MscS in Xenopus laevis oocytes.
2011,
Pubmed
,
Xenbase
Mari,
Gating of the MlotiK1 potassium channel involves large rearrangements of the cyclic nucleotide-binding domains.
2011,
Pubmed
Marques-Carvalho,
Structural, biochemical, and functional characterization of the cyclic nucleotide binding homology domain from the mouse EAG1 potassium channel.
2012,
Pubmed
Nache,
Activation of olfactory-type cyclic nucleotide-gated channels is highly cooperative.
2005,
Pubmed
,
Xenbase
Nache,
Differential regulation by cyclic nucleotides of the CNGA4 and CNGB1b subunits in olfactory cyclic nucleotide-gated channels.
2012,
Pubmed
Nimigean,
A cyclic nucleotide modulated prokaryotic K+ channel.
2004,
Pubmed
Nimigean,
Ligand binding and activation in a prokaryotic cyclic nucleotide-modulated channel.
2007,
Pubmed
Picardeau,
Genome sequence of the saprophyte Leptospira biflexa provides insights into the evolution of Leptospira and the pathogenesis of leptospirosis.
2008,
Pubmed
Rath,
Detergent binding explains anomalous SDS-PAGE migration of membrane proteins.
2009,
Pubmed
Robinson,
Hyperpolarization-activated cation currents: from molecules to physiological function.
2003,
Pubmed
Shabb,
Cyclic nucleotide-binding domains in proteins having diverse functions.
1992,
Pubmed
Shi,
Atomic structure of a Na+- and K+-conducting channel.
2006,
Pubmed
Thon,
Elementary functional properties of single HCN2 channels.
2013,
Pubmed
,
Xenbase
Tibbs,
A state-independent interaction between ligand and a conserved arginine residue in cyclic nucleotide-gated channels reveals a functional polarity of the cyclic nucleotide binding site.
1998,
Pubmed
,
Xenbase
Wong,
Ligand-binding domain subregions contributing to bimodal agonism in cyclic nucleotide-gated channels.
2011,
Pubmed
,
Xenbase
Xu,
Structural basis for the cAMP-dependent gating in the human HCN4 channel.
2010,
Pubmed
,
Xenbase
Xu,
Local and global interpretations of a disease-causing mutation near the ligand entry path in hyperpolarization-activated cAMP-gated channel.
2012,
Pubmed
,
Xenbase
Young,
Efficient coupling of ligand binding to channel opening by the binding domain of a modulatory (beta) subunit of the olfactory cyclic nucleotide-gated channel.
2001,
Pubmed
,
Xenbase
Zagotta,
Structural basis for modulation and agonist specificity of HCN pacemaker channels.
2003,
Pubmed
