IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-40058-7.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-40058-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-40058-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. 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.
    3. 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.
    4. 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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Camden M. Driggers & Yi-Ying Kuo & Phillip Zhu & Assmaa ElSheikh & Show-Ling Shyng, 2024. "Structure of an open KATP channel reveals tandem PIP2 binding sites mediating the Kir6.2 and SUR1 regulatory interface," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Martina Nicoletti & Letizia Chiodo & Alessandro Loppini, 2021. "Biophysics and Modeling of Mechanotransduction in Neurons: A Review," Mathematics, MDPI, vol. 9(4), pages 1-32, February.
    3. Mengmeng Wang & Jing-Xiang Wu & Dian Ding & Lei Chen, 2022. "Structural insights into the mechanism of pancreatic KATP channel regulation by nucleotides," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    4. Willow Coyote-Maestas & David Nedrud & Antonio Suma & Yungui He & Kenneth A. Matreyek & Douglas M. Fowler & Vincenzo Carnevale & Chad L. Myers & Daniel Schmidt, 2021. "Probing ion channel functional architecture and domain recombination compatibility by massively parallel domain insertion profiling," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    5. Marcos Matamoros & Xue Wen Ng & Joshua B. Brettmann & David W. Piston & Colin G. Nichols, 2023. "Conformational plasticity of NaK2K and TREK2 potassium channel selectivity filters," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40058-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.