Reciprocal voltage sensor-to-pore coupling leads to potassium channel C-type inactivation
| Autor: | Jakob Renhorn, Fredrik Elinder, Erik Lindahl, Sara I. Liin, Luca Conti, Anders Gabrielsson, Fredrik Turesson |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
congenital hereditary and neonatal diseases and abnormalities Materials science Potassium Static Electricity chemistry.chemical_element Molecular Dynamics Simulation Article Membrane Potentials Ion Xenopus laevis 03 medical and health sciences 0302 clinical medicine Protein Domains Structural Biology Animals Strukturbiologi Membrane potential Multidisciplinary Depolarization Voltage-gated potassium channel Potassium channel Coupling (electronics) 030104 developmental biology Membrane chemistry Biochemistry Mutation Shaker Superfamily of Potassium Channels Biophysics Ion Channel Gating Gene Deletion 030217 neurology & neurosurgery Cadmium |
| Zdroj: | Scientific Reports |
| Popis: | Voltage-gated potassium channels open at depolarized membrane voltages. A prolonged depolarization causes a rearrangement of the selectivity filter which terminates the conduction of ions - a process called slow or C-type inactivation. How structural rearrangements in the voltage-sensor domain (VSD) cause alteration in the selectivity filter, and vice versa, are not fully understood. We show that pulling the pore domain of the Shaker potassium channel towards the VSD by a Cd2+ bridge accelerates C-type inactivation. Molecular dynamics simulations show that such pulling widens the selectivity filter and disrupts the K+ coordination, a hallmark for C-type inactivation. An engineered Cd2+ bridge within the VSD also affect C-type inactivation. Conversely, a pore domain mutation affects VSD gating-charge movement. Finally, C-type inactivation is caused by the concerted action of distant amino acid residues in the pore domain. All together, these data suggest a reciprocal communication between the pore domain and the VSD in the extracellular portion of the channel. Funding Agencies|Swedish Research Council; Swedish Brain Foundation; Swedish Heart-Lung Foundation; Swedish e-Science Research Center; Foundation Blanceflor Boncompagni Ludovisi, nee Bildt |
| Databáze: | OpenAIRE |
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