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  • 1. Conti, Luca
    et al.
    Renhorn, Jakob
    Gabrielsson, Anders
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical & Computational Biophysics.
    Turesson, Fredrik
    Liin, Sara I.
    Lindahl, Erik
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical & Computational Biophysics. Stockholm University, Sweden.
    Elinder, Fredrik
    Reciprocal voltage sensor-to-pore coupling leads to potassium channel C-type inactivation2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 27562Article in journal (Refereed)
    Abstract [en]

    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.

  • 2. Conti, Luca
    et al.
    Renhorn, Jakob
    Gabrielsson, Anders
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical & Computational Biophysics.
    Turesson, Fredrik
    Liin, Sara
    Lindahl, Erik
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical & Computational Biophysics.
    Elinder, Fredrik
    A Reciprocal Voltage Sensor-To-Pore Coupling in C-Type Inactivation2016In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 110, no 3, p. 104A-104AArticle in journal (Other academic)
  • 3.
    Gabrielsson, Anders
    et al.
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical & Computational Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Liin, Sara
    Elinder, Fredrik
    Lindahl, Erik
    Binding Structure & Dynamics for Toxins Modifying the Gating Mechanism of Kv Channels2014In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 106, no 2, p. 738A-738AArticle in journal (Other academic)
  • 4. Liin, Sara
    et al.
    Gabrielsson, Anders
    KTH, Centres, SeRC - Swedish e-Science Research Centre.
    Elinder, Fredrik
    Lindahl, Erik
    The Molecular Mechanism of the Dual Spider Toxin Effect on Voltage Gated K+ Channels2016In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 110, no 3, p. 107A-107AArticle in journal (Other academic)
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