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Proc Natl Acad Sci U S A
2020 Apr 28;11717:9365-9376. doi: 10.1073/pnas.1916166117.
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Determining the correct stoichiometry of Kv2.1/Kv6.4 heterotetramers, functional in multiple stoichiometrical configurations.
Möller L
,
Regnier G
,
Labro AJ
,
Blunck R
,
Snyders DJ
.
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The electrically silent (KvS) members of the voltage-gated potassium (Kv) subfamilies Kv5, Kv6, Kv8, and Kv9 selectively modulate Kv2 subunits by forming heterotetrameric Kv2/KvS channels. Based on the reported 3:1 stoichiometry of Kv2.1/Kv9.3 channels, we tested the hypothesis that Kv2.1/Kv6.4 channels express, in contrast to the assumed 3:1, in a 2:2 stoichiometry. We investigate the Kv2.1/Kv6.4 stoichiometry using single subunit counting and functional characterization of tetrameric concatemers. For selecting the most probable stoichiometry, we introduce a model-selection method that is applicable for any multimeric complex by investigating the stoichiometry of Kv2.1/Kv6.4 channels. Weighted likelihood calculations bring rigor to a powerful technique. Using the weighted-likelihood model-selection method and analysis of electrophysiological data, we show that Kv2.1/Kv6.4 channels express, in contrast to the assumed 3:1, in a 2:2 stoichiometry. Within this stoichiometry, the Kv6.4 subunits have to be positioned alternating with Kv2.1 to express functional channels. The variability in Kv2/KvS assembly increases the diversity of heterotetrameric configurations and extends the regulatory possibilities of KvS by allowing the presence of more than one silent subunit.
Al-Sabi,
Arrangement of Kv1 alpha subunits dictates sensitivity to tetraethylammonium.
2010, Pubmed
Al-Sabi,
Arrangement of Kv1 alpha subunits dictates sensitivity to tetraethylammonium.
2010,
Pubmed
Al-Sabi,
Pharmacological characteristics of Kv1.1- and Kv1.2-containing channels are influenced by the stoichiometry and positioning of their α subunits.
2013,
Pubmed
,
Xenbase
Batulan,
An intersubunit interaction between S4-S5 linker and S6 is responsible for the slow off-gating component in Shaker K+ channels.
2010,
Pubmed
Bocksteins,
Electrically silent Kv subunits: their molecular and functional characteristics.
2012,
Pubmed
Bocksteins,
Conserved negative charges in the N-terminal tetramerization domain mediate efficient assembly of Kv2.1 and Kv2.1/Kv6.4 channels.
2009,
Pubmed
Bocksteins,
The subfamily-specific interaction between Kv2.1 and Kv6.4 subunits is determined by interactions between the N- and C-termini.
2014,
Pubmed
Bocksteins,
Kv5, Kv6, Kv8, and Kv9 subunits: No simple silent bystanders.
2016,
Pubmed
Bocksteins,
The electrically silent Kv6.4 subunit confers hyperpolarized gating charge movement in Kv2.1/Kv6.4 heterotetrameric channels.
2012,
Pubmed
David,
Auxiliary KCNE subunits modulate both homotetrameric Kv2.1 and heterotetrameric Kv2.1/Kv6.4 channels.
2015,
Pubmed
Dunsing,
Optimal fluorescent protein tags for quantifying protein oligomerization in living cells.
2018,
Pubmed
Durisic,
Single-molecule evaluation of fluorescent protein photoactivation efficiency using an in vivo nanotemplate.
2014,
Pubmed
,
Xenbase
Durisic,
Stoichiometry of the human glycine receptor revealed by direct subunit counting.
2012,
Pubmed
,
Xenbase
Fricke,
One, two or three? Probing the stoichiometry of membrane proteins by single-molecule localization microscopy.
2015,
Pubmed
Godin,
Spatial Intensity Distribution Analysis Reveals Abnormal Oligomerization of Proteins in Single Cells.
2015,
Pubmed
Gutman,
International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels.
2005,
Pubmed
Heginbotham,
The aromatic binding site for tetraethylammonium ion on potassium channels.
1992,
Pubmed
Jegla,
A novel subunit for shal K+ channels radically alters activation and inactivation.
1997,
Pubmed
Kang,
Spectrum of KV 2.1 Dysfunction in KCNB1-Associated Neurodevelopmental Disorders.
2019,
Pubmed
Kavanaugh,
Multiple subunits of a voltage-dependent potassium channel contribute to the binding site for tetraethylammonium.
1992,
Pubmed
,
Xenbase
Kerschensteiner,
Fluorescence measurements reveal stoichiometry of K+ channels formed by modulatory and delayed rectifier alpha-subunits.
2005,
Pubmed
Kitazawa,
Kv4.2 and accessory dipeptidyl peptidase-like protein 10 (DPP10) subunit preferentially form a 4:2 (Kv4.2:DPP10) channel complex.
2015,
Pubmed
,
Xenbase
Kitazawa,
The stoichiometry and biophysical properties of the Kv4 potassium channel complex with K+ channel-interacting protein (KChIP) subunits are variable, depending on the relative expression level.
2014,
Pubmed
,
Xenbase
Lee,
Structural determinant for assembly of mammalian K+ channels.
1994,
Pubmed
,
Xenbase
Li,
Specification of subunit assembly by the hydrophilic amino-terminal domain of the Shaker potassium channel.
1992,
Pubmed
Li,
α-SNAP regulates dynamic, on-site assembly and calcium selectivity of Orai1 channels.
2016,
Pubmed
Liesche,
Automated Analysis of Single-Molecule Photobleaching Data by Statistical Modeling of Spot Populations.
2015,
Pubmed
Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase
Lu,
T1-T1 interactions occur in ER membranes while nascent Kv peptides are still attached to ribosomes.
2001,
Pubmed
,
Xenbase
MacKinnon,
Mutations affecting TEA blockade and ion permeation in voltage-activated K+ channels.
1990,
Pubmed
McCormack,
Tandem linkage of Shaker K+ channel subunits does not ensure the stoichiometry of expressed channels.
1992,
Pubmed
,
Xenbase
McGuire,
Automating single subunit counting of membrane proteins in mammalian cells.
2012,
Pubmed
,
Xenbase
Mederos Y Schnitzler,
Mutation of histidine 105 in the T1 domain of the potassium channel Kv2.1 disrupts heteromerization with Kv6.3 and Kv6.4.
2009,
Pubmed
Minassian,
Altered Kv3.3 channel gating in early-onset spinocerebellar ataxia type 13.
2012,
Pubmed
,
Xenbase
Nagata,
ABCA1 dimer-monomer interconversion during HDL generation revealed by single-molecule imaging.
2013,
Pubmed
Nakajo,
Stoichiometry of the KCNQ1 - KCNE1 ion channel complex.
2010,
Pubmed
,
Xenbase
Naso,
Stoichiometry studies reveal functional properties of KDC1 in plant shaker potassium channels.
2006,
Pubmed
,
Xenbase
Ottschytsch,
Obligatory heterotetramerization of three previously uncharacterized Kv channel alpha-subunits identified in the human genome.
2002,
Pubmed
Ottschytsch,
Domain analysis of Kv6.3, an electrically silent channel.
2005,
Pubmed
Pisupati,
The S6 gate in regulatory Kv6 subunits restricts heteromeric K+ channel stoichiometry.
2018,
Pubmed
,
Xenbase
Post,
Kv2.1 and electrically silent Kv6.1 potassium channel subunits combine and express a novel current.
1996,
Pubmed
,
Xenbase
Powers,
A perspective on mechanisms of protein tetramer formation.
2003,
Pubmed
Shapiro,
Stoichiometry and arrangement of heteromeric olfactory cyclic nucleotide-gated ion channels.
1998,
Pubmed
,
Xenbase
Shen,
Deletion analysis of K+ channel assembly.
1993,
Pubmed
,
Xenbase
Shen,
Molecular recognition and assembly sequences involved in the subfamily-specific assembly of voltage-gated K+ channel subunit proteins.
1995,
Pubmed
Stas,
Modulation of Closed-State Inactivation in Kv2.1/Kv6.4 Heterotetramers as Mechanism for 4-AP Induced Potentiation.
2015,
Pubmed
Stewart,
The Kv7.2/Kv7.3 heterotetramer assembles with a random subunit arrangement.
2012,
Pubmed
Stocker,
Subunit assembly and domain analysis of electrically silent K+ channel alpha-subunits of the rat Kv9 subfamily.
1999,
Pubmed
,
Xenbase
Tu,
Evidence for dimerization of dimers in K+ channel assembly.
1999,
Pubmed
,
Xenbase
Tu,
Voltage-gated K+ channels contain multiple intersubunit association sites.
1996,
Pubmed
,
Xenbase
Ulbrich,
Subunit counting in membrane-bound proteins.
2007,
Pubmed
,
Xenbase
Vandenberg,
Inactivation viewed through single sodium channels.
1984,
Pubmed
Wagenmakers,
AIC model selection using Akaike weights.
2004,
Pubmed
Wong,
Plasma membrane dynamics and tetrameric organisation of ABCG2 transporters in mammalian cells revealed by single particle imaging techniques.
2016,
Pubmed
Xu,
Assembly of voltage-gated potassium channels. Conserved hydrophilic motifs determine subfamily-specific interactions between the alpha-subunits.
1995,
Pubmed
Yu,
Dynamic subunit stoichiometry confers a progressive continuum of pharmacological sensitivity by KCNQ potassium channels.
2013,
Pubmed
Yu,
Structural and molecular basis of the assembly of the TRPP2/PKD1 complex.
2009,
Pubmed
,
Xenbase
