72 results found
    1. Structural Biology and Molecular Biophysics

    Allosteric mechanism for KCNE1 modulation of KCNQ1 potassium channel activation

    Georg Kuenze et al.
    An integrative structural biology approach provides refined models of the KCNQ1-KCNE1 channel complex, which propose a new mechanism to explain how KCNE1 modulates KCNQ1 channel activation.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Unnatural amino acid photo-crosslinking of the IKs channel complex demonstrates a KCNE1:KCNQ1 stoichiometry of up to 4:4

    Christopher I Murray et al.
    The IKs potassium channel complex displays functional flexibility that depends on the ratio of its constituent KCNQ1 and KCNE1 protein subunits.
    1. Structural Biology and Molecular Biophysics

    Structure and physiological function of the human KCNQ1 channel voltage sensor intermediate state

    Keenan C Taylor et al.
    The intermediate state conformation of the human KCNQ1 potassium channel voltage sensor domain was determined, validated, and shown to be conductive under physiological conditions.
    1. Structural Biology and Molecular Biophysics

    KCNE1 tunes the sensitivity of KV7.1 to polyunsaturated fatty acids by moving turret residues close to the binding site

    Johan E Larsson et al.
    An auxiliary subunit alters the effect of a family of small-molecule openers on a voltage-gated potassium channel by inducing structural re-arrangements that promote protonation of the drug molecule.
    1. Structural Biology and Molecular Biophysics

    ML277 specifically enhances the fully activated open state of KCNQ1 by modulating VSD-pore coupling

    Panpan Hou et al.
    ML277 exclusively enhances the AO state voltage-sensing domain (VSD)-pore coupling of KCNQ1 channels, providing an effective tool to investigate the voltge-dependent gating and new strategies for treating long QT syndrome.
    1. Structural Biology and Molecular Biophysics

    Domain–domain interactions determine the gating, permeation, pharmacology, and subunit modulation of the IKs ion channel

    Mark A Zaydman et al.
    Contrary to a generally accepted principle, the pore properties of KCNQ1 channels depend on the states of voltage-sensing domains activation; KCNE1 alters the voltage-sensing domains-pore coupling to modulate KCNQ1 channel properties.
    1. Structural Biology and Molecular Biophysics

    Fatty acid analogue N-arachidonoyl taurine restores function of IKs channels with diverse long QT mutations

    Sara I Liin et al.
    Fatty acid analogues are interesting prototype compounds that may inspire the development of future IKs channel activators to treat patients with long QT syndrome caused by diverse arrhythmia-causing mutations in the IKs channel.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    Opposing roles for DNA replication initiator proteins ORC1 and CDC6 in control of Cyclin E gene transcription

    Manzar Hossain, Bruce Stillman
    Two related DNA replication initiation proteins contribute to the decision of whether to enter a new round of the cell division cycle or enter into a period of proliferative quiescence.
    1. Structural Biology and Molecular Biophysics

    Polyunsaturated fatty acid analogues differentially affect cardiac NaV, CaV, and KV channels through unique mechanisms

    Briana M Bohannon et al.
    Polyunsaturated fatty acid analogues show selectivity for different cardiac ion channels, suggesting their potential use for the treatment of different subtypes of Long QT Syndrome.
    1. Structural Biology and Molecular Biophysics
    2. Cell Biology

    Sculpting ion channel functional expression with engineered ubiquitin ligases

    Scott A Kanner et al.
    Engineered E3 ubiquitin ligases are utilized to elucidate mechanisms underlying ubiquitin regulation of membrane proteins, and to achieve robust post-translational functional knockdown of ion channels.

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