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The degenerin region of the human bile acid-sensitive ion channel (BASIC) is involved in channel inhibition by calcium and activation by bile acids.
Ilyaskin AV
,
Kirsch SA
,
Böckmann RA
,
Sticht H
,
Korbmacher C
,
Haerteis S
,
Diakov A
.
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The bile acid-sensitive ion channel (BASIC) is a member of the ENaC/degenerin family of ion channels. It is activated by bile acids and inhibited by extracellular Ca2+. The aim of this study was to explore the molecular mechanisms mediating these effects. The modulation of BASIC function by extracellular Ca2+ and tauro-deoxycholic acid (t-DCA) was studied in Xenopus laevis oocytes heterologously expressing human BASIC using the two-electrode voltage-clamp and outside-out patch-clamp techniques. Substitution of aspartate D444 to alanine or cysteine in the degenerin region of BASIC, a region known to be critically involved in channel gating, resulted in a substantial reduction of BASIC Ca2+ sensitivity. Moreover, mutating D444 or the neighboring alanine (A443) to cysteine significantly reduced the t-DCA-mediated BASIC stimulation. A combined molecular docking/simulation approach demonstrated that t-DCA may temporarily form hydrogen bonds with several amino acid residues including D444 in the outer vestibule of the BASIC pore or in the inter-subunit space. By these interactions, t-DCA may stabilize the open state of the channel. Indeed, single-channel recordings provided evidence that t-DCA activates BASIC by stabilizing the open state of the channel, whereas extracellular Ca2+ inhibits BASIC by stabilizing its closed state. In conclusion, our results highlight the potential role of the degenerin region as a critical regulatory site involved in the functional interaction of Ca2+ and t-DCA with BASIC.
Arnold,
The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling.
2006, Pubmed
Arnold,
The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling.
2006,
Pubmed
Baconguis,
Structural plasticity and dynamic selectivity of acid-sensing ion channel-spider toxin complexes.
2012,
Pubmed
Baconguis,
X-ray structure of acid-sensing ion channel 1-snake toxin complex reveals open state of a Na(+)-selective channel.
2014,
Pubmed
Biasini,
SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information.
2014,
Pubmed
Bussi,
Canonical sampling through velocity rescaling.
2007,
Pubmed
Chen,
Interfacial molecular organization at aqueous solution surfaces of atmospherically relevant dimethyl sulfoxide and methanesulfonic Acid using sum frequency spectroscopy and molecular dynamics simulation.
2010,
Pubmed
Dawson,
Structure of the acid-sensing ion channel 1 in complex with the gating modifier Psalmotoxin 1.
2012,
Pubmed
de Jong,
Improved Parameters for the Martini Coarse-Grained Protein Force Field.
2013,
Pubmed
Diakov,
A novel pathway of epithelial sodium channel activation involves a serum- and glucocorticoid-inducible kinase consensus motif in the C terminus of the channel's alpha-subunit.
2004,
Pubmed
,
Xenbase
Diakov,
Protein kinase B alpha (PKBα) stimulates the epithelial sodium channel (ENaC) heterologously expressed in Xenopus laevis oocytes by two distinct mechanisms.
2010,
Pubmed
,
Xenbase
Diakov,
Cleavage in the {gamma}-subunit of the epithelial sodium channel (ENaC) plays an important role in the proteolytic activation of near-silent channels.
2008,
Pubmed
,
Xenbase
Dickson,
Lipid14: The Amber Lipid Force Field.
2014,
Pubmed
Fujimoto,
Modulation of the FMRFamide-gated Na+ channel by external Ca2.
2017,
Pubmed
,
Xenbase
Gonzales,
Pore architecture and ion sites in acid-sensing ion channels and P2X receptors.
2009,
Pubmed
Guex,
Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer: a historical perspective.
2009,
Pubmed
Haerteis,
The delta-subunit of the epithelial sodium channel (ENaC) enhances channel activity and alters proteolytic ENaC activation.
2009,
Pubmed
,
Xenbase
Haerteis,
Proteolytic activation of the human epithelial sodium channel by trypsin IV and trypsin I involves distinct cleavage sites.
2014,
Pubmed
,
Xenbase
Ilyaskin,
Activation of the Human Epithelial Sodium Channel (ENaC) by Bile Acids Involves the Degenerin Site.
2016,
Pubmed
,
Xenbase
Ilyaskin,
Bile acids potentiate proton-activated currents in Xenopus laevis oocytes expressing human acid-sensing ion channel (ASIC1a).
2017,
Pubmed
,
Xenbase
Ilyaskin,
The degenerin region of the human bile acid-sensitive ion channel (BASIC) is involved in channel inhibition by calcium and activation by bile acids.
2018,
Pubmed
,
Xenbase
Irwin,
ZINC--a free database of commercially available compounds for virtual screening.
2005,
Pubmed
Jasti,
Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH.
2007,
Pubmed
Kellenberger,
International Union of Basic and Clinical Pharmacology. XCI. structure, function, and pharmacology of acid-sensing ion channels and the epithelial Na+ channel.
2015,
Pubmed
Kiefer,
The SWISS-MODEL Repository and associated resources.
2009,
Pubmed
Korbmacher,
A calcium-activated and nucleotide-sensitive nonselective cation channel in M-1 mouse cortical collecting duct cells.
1995,
Pubmed
Lefèvre,
Pharmacological and electrophysiological characterization of the human bile acid-sensitive ion channel (hBASIC).
2014,
Pubmed
Lindorff-Larsen,
Improved side-chain torsion potentials for the Amber ff99SB protein force field.
2010,
Pubmed
Madej,
A Parameterization of Cholesterol for Mixed Lipid Bilayer Simulation within the Amber Lipid14 Force Field.
2015,
Pubmed
Morris,
AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility.
2009,
Pubmed
Paukert,
Identification of the Ca2+ blocking site of acid-sensing ion channel (ASIC) 1: implications for channel gating.
2004,
Pubmed
,
Xenbase
Pluhackova,
A Critical Comparison of Biomembrane Force Fields: Structure and Dynamics of Model DMPC, POPC, and POPE Bilayers.
2016,
Pubmed
Rauh,
A mutation of the epithelial sodium channel associated with atypical cystic fibrosis increases channel open probability and reduces Na+ self inhibition.
2010,
Pubmed
,
Xenbase
Sakai,
Cloning and functional expression of a novel degenerin-like Na+ channel gene in mammals.
1999,
Pubmed
,
Xenbase
Sanner,
Python: a programming language for software integration and development.
1999,
Pubmed
Schaefer,
Molecular cloning, functional expression and chromosomal localization of an amiloride-sensitive Na(+) channel from human small intestine.
2000,
Pubmed
,
Xenbase
Schmidt,
The bile acid-sensitive ion channel (BASIC) is activated by alterations of its membrane environment.
2014,
Pubmed
,
Xenbase
Schmidt,
A Cytosolic Amphiphilic α-Helix Controls the Activity of the Bile Acid-sensitive Ion Channel (BASIC).
2016,
Pubmed
,
Xenbase
Siu,
Optimization of the OPLS-AA Force Field for Long Hydrocarbons.
2012,
Pubmed
Trott,
AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading.
2010,
Pubmed
Wassenaar,
Computational Lipidomics with insane: A Versatile Tool for Generating Custom Membranes for Molecular Simulations.
2015,
Pubmed
Wassenaar,
Going Backward: A Flexible Geometric Approach to Reverse Transformation from Coarse Grained to Atomistic Models.
2014,
Pubmed
Wiemuth,
BASIC--a bile acid-sensitive ion channel highly expressed in bile ducts.
2012,
Pubmed
Wiemuth,
Bile acids increase the activity of the epithelial Na+ channel.
2014,
Pubmed
,
Xenbase
Wiemuth,
The pharmacological profile of brain liver intestine Na+ channel: inhibition by diarylamidines and activation by fenamates.
2011,
Pubmed
,
Xenbase
Wiemuth,
Strong activation of bile acid-sensitive ion channel (BASIC) by ursodeoxycholic acid.
2013,
Pubmed
Yesylevskyy,
Polarizable water model for the coarse-grained MARTINI force field.
2010,
Pubmed
