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Subunit gating resulting from individual protonation events in Kir2 channels

Author

Listed:
  • Grigory Maksaev

    (Washington University School of Medicine)

  • Michael Bründl-Jirout

    (University of Vienna)

  • Anna Stary-Weinzinger

    (University of Vienna)

  • Eva-Maria Zangerl-Plessl

    (University of Vienna)

  • Sun-Joo Lee

    (Washington University School of Medicine)

  • Colin G. Nichols

    (Washington University School of Medicine)

Abstract

Inwardly rectifying potassium (Kir) channels open at the ‘helix bundle crossing’ (HBC), formed by the M2 helices at the cytoplasmic end of the transmembrane pore. Introduced negative charges at the HBC (G178D) in Kir2.2 channels forces opening, allowing pore wetting and free movement of permeant ions between the cytoplasm and the inner cavity. Single-channel recordings reveal striking, pH-dependent, subconductance behaviors in G178D (or G178E and equivalent Kir2.1[G177E]) mutant channels, with well-resolved non-cooperative subconductance levels. Decreasing cytoplasmic pH shifts the probability towards lower conductance levels. Molecular dynamics simulations show how protonation of Kir2.2[G178D], or the D173 pore-lining residues, changes solvation, K+ ion occupancy, and K+ conductance. Ion channel gating and conductance are classically understood as separate processes. The present data reveal how individual protonation events change the electrostatic microenvironment of the pore, resulting in step-wise alterations of ion pooling, and hence conductance, that appear as ‘gated’ substates.

Suggested Citation

  • Grigory Maksaev & Michael Bründl-Jirout & Anna Stary-Weinzinger & Eva-Maria Zangerl-Plessl & Sun-Joo Lee & Colin G. Nichols, 2023. "Subunit gating resulting from individual protonation events in Kir2 channels," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40058-7
    DOI: 10.1038/s41467-023-40058-7
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    References listed on IDEAS

    as
    1. Sun-Joo Lee & Shizhen Wang & William Borschel & Sarah Heyman & Jacob Gyore & Colin G. Nichols, 2013. "Secondary anionic phospholipid binding site and gating mechanism in Kir2.1 inward rectifier channels," Nature Communications, Nature, vol. 4(1), pages 1-12, December.
    2. Scott B. Hansen & Xiao Tao & Roderick MacKinnon, 2011. "Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2," Nature, Nature, vol. 477(7365), pages 495-498, September.
    3. Gisela D. Cymes & Claudio Grosman, 2011. "Tunable pKa values and the basis of opposite charge selectivities in nicotinic-type receptors," Nature, Nature, vol. 474(7352), pages 526-530, June.
    4. Gisela D. Cymes & Ying Ni & Claudio Grosman, 2005. "Probing ion-channel pores one proton at a time," Nature, Nature, vol. 438(7070), pages 975-980, December.
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