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
2008 Feb 05;1055:1478-82. doi: 10.1073/pnas.0710366105.
Show Gene links
Show Anatomy links
Counting membrane-embedded KCNE beta-subunits in functioning K+ channel complexes.
Morin TJ
,
Kobertz WR
.
???displayArticle.abstract???
Ion channels are multisubunit proteins responsible for the generation and propagation of action potentials in nerve, skeletal muscle, and heart as well as maintaining salt and water homeostasis in epithelium. The subunit composition and stoichiometry of these membrane protein complexes underlies their physiological function, as different cells pair ion-conducting alpha-subunits with specific regulatory beta-subunits to produce complexes with diverse ion-conducting and gating properties. However, determining the number of alpha- and beta-subunits in functioning ion channel complexes is challenging and often fraught with contradictory results. Here we describe the synthesis of a chemically releasable, irreversible K(+) channel inhibitor and its iterative application to tally the number of beta-subunits in a KCNQ1/KCNE1 K(+) channel complex. Using this inhibitor in electrical recordings, we definitively show that there are two KCNE subunits in a functioning tetrameric K(+) channel, breaking the apparent fourfold arrangement of the ion-conducting subunits. This digital determination rules out any measurable contribution from supra, sub, and multiple stoichiometries, providing a uniform structural picture to interpret KCNE beta-subunit modulation of voltage-gated K(+) channels and the inherited mutations that cause dysfunction. Moreover, the architectural asymmetry of the K(+) channel complex affords a unique opportunity to therapeutically target ion channels that coassemble with KCNE beta-subunits.
Barany,
A new amino protecting group removable by reduction. Chemistry of the dithiasuccinoyl (Dts) function.
1977, Pubmed
Barany,
A new amino protecting group removable by reduction. Chemistry of the dithiasuccinoyl (Dts) function.
1977,
Pubmed
Blaustein,
Kinetics of tethering quaternary ammonium compounds to K(+) channels.
2002,
Pubmed
,
Xenbase
Chandrasekhar,
KCNE1 subunits require co-assembly with K+ channels for efficient trafficking and cell surface expression.
2006,
Pubmed
Chen,
Charybdotoxin binding in the I(Ks) pore demonstrates two MinK subunits in each channel complex.
2003,
Pubmed
,
Xenbase
Chen,
Serial perturbation of MinK in IKs implies an alpha-helical transmembrane span traversing the channel corpus.
2007,
Pubmed
,
Xenbase
Goldin,
Maintenance of Xenopus laevis and oocyte injection.
1992,
Pubmed
,
Xenbase
Goldstein,
The charybdotoxin receptor of a Shaker K+ channel: peptide and channel residues mediating molecular recognition.
1994,
Pubmed
,
Xenbase
Gordon,
Endogenous KCNE subunits govern Kv2.1 K+ channel activation kinetics in Xenopus oocyte studies.
2006,
Pubmed
,
Xenbase
Kobertz,
K+ channels lacking the 'tetramerization' domain: implications for pore structure.
1999,
Pubmed
,
Xenbase
Krafte,
Use of stage II-III Xenopus oocytes to study voltage-dependent ion channels.
1992,
Pubmed
,
Xenbase
Krumerman,
An LQT mutant minK alters KvLQT1 trafficking.
2004,
Pubmed
Levitsky,
Exo-mechanism proximity-accelerated alkylations: investigations of linkers, electrophiles and surface mutations in engineered cyclophilin-cyclosporin systems.
2005,
Pubmed
Lu,
T1-T1 interactions occur in ER membranes while nascent Kv peptides are still attached to ribosomes.
2001,
Pubmed
,
Xenbase
Lu,
Mapping the electrostatic potential within the ribosomal exit tunnel.
2007,
Pubmed
MacKinnon,
Structural conservation in prokaryotic and eukaryotic potassium channels.
1998,
Pubmed
McCrossan,
The MinK-related peptides.
2004,
Pubmed
,
Xenbase
Morin,
A derivatized scorpion toxin reveals the functional output of heteromeric KCNQ1-KCNE K+ channel complexes.
2007,
Pubmed
,
Xenbase
Powers,
A perspective on mechanisms of protein tetramer formation.
2003,
Pubmed
Salata,
A novel benzodiazepine that activates cardiac slow delayed rectifier K+ currents.
1998,
Pubmed
,
Xenbase
Sanguinetti,
Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel.
1996,
Pubmed
,
Xenbase
Schwake,
A carboxy-terminal domain determines the subunit specificity of KCNQ K+ channel assembly.
2003,
Pubmed
,
Xenbase
Shimony,
Engineering a uniquely reactive thiol into a cysteine-rich peptide.
1994,
Pubmed
Smith,
Purification of charybdotoxin, a specific inhibitor of the high-conductance Ca2+-activated K+ channel.
1986,
Pubmed
Soreq,
Xenopus oocyte microinjection: from gene to protein.
1992,
Pubmed
,
Xenbase
Splawski,
Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2.
2000,
Pubmed
Stühmer,
Electrophysiological recording from Xenopus oocytes.
1992,
Pubmed
,
Xenbase
Swanson,
In vitro synthesis of RNA for expression of ion channels in Xenopus oocytes.
1992,
Pubmed
,
Xenbase
Tu,
Evidence for dimerization of dimers in K+ channel assembly.
1999,
Pubmed
,
Xenbase
Tyson,
Mutational spectrum in the cardioauditory syndrome of Jervell and Lange-Nielsen.
2000,
Pubmed
Tzounopoulos,
min K channels form by assembly of at least 14 subunits.
1995,
Pubmed
,
Xenbase
Wang,
Subunit composition of minK potassium channels.
1995,
Pubmed
,
Xenbase
Wang,
MinK-KvLQT1 fusion proteins, evidence for multiple stoichiometries of the assembled IsK channel.
1998,
Pubmed
