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Effect of Sensor Domain Mutations on the Properties of Voltage-Gated Ion Channels: Molecular Dynamics Studies of the Potassium Channel Kv1.2
- Source :
- Biophysical Journal. 99(9):L72-L74
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
Abstract
- The effects on the structural and functional properties of the Kv1.2 voltage-gated ion channel, caused by selective mutation of voltage sensor domain residues, have been investigated using classical molecular dynamics simulations. Following experiments that have identified mutations of voltage-gated ion channels involved in state-dependent omega currents, we observe for both the open and closed conformations of the Kv1.2 that specific mutations of S4 gating-charge residues destabilize the electrostatic network between helices of the voltage sensor domain, resulting in the formation of hydrophilic pathways linking the intra- and extracellular media. When such mutant channels are subject to transmembrane potentials, they conduct cations via these so-called “omega pores.” This study provides therefore further insight into the molecular mechanisms that lead to omega currents, which have been linked to certain channelopathies.
- Subjects :
- Models, Molecular
Protein Conformation
Molecular Sequence Data
Static Electricity
Biophysics
In Vitro Techniques
Molecular Dynamics Simulation
medicine.disease_cause
Biophysical Phenomena
Membrane Potentials
Molecular dynamics
Protein structure
Static electricity
Kv1.2 Potassium Channel
medicine
Humans
Amino Acid Sequence
Ion channel
Membrane potential
Mutation
Sequence Homology, Amino Acid
Voltage-gated ion channel
Biophysical Letter
Chemistry
Potassium channel
Protein Structure, Tertiary
Amino Acid Substitution
Biochemistry
Mutagenesis, Site-Directed
Mutant Proteins
Hydrophobic and Hydrophilic Interactions
Ion Channel Gating
Subjects
Details
- ISSN :
- 00063495
- Volume :
- 99
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Biophysical Journal
- Accession number :
- edsair.doi.dedup.....0e39877a768e1f9c0ad0a35748a561c0
- Full Text :
- https://doi.org/10.1016/j.bpj.2010.08.069