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A short intrinsically disordered region at KtrB’s N-terminus facilitates allosteric regulation of K+ channel KtrAB

Author

Listed:
  • Janina Stautz

    (Goethe University Frankfurt)

  • David Griwatz

    (Goethe University Frankfurt)

  • Susann Kaltwasser

    (Max Planck Institute of Biophysics)

  • Ahmad Reza Mehdipour

    (Ghent University
    Max Planck Institute of Biophysics)

  • Sophie Ketter

    (Goethe University Frankfurt)

  • Celina Thiel

    (Goethe University Frankfurt)

  • Dorith Wunnicke

    (Goethe University Frankfurt)

  • Marina Schrecker

    (Goethe University Frankfurt)

  • Deryck J. Mills

    (Max Planck Institute of Biophysics)

  • Gerhard Hummer

    (Max Planck Institute of Biophysics
    Goethe University Frankfurt)

  • Janet Vonck

    (Max Planck Institute of Biophysics)

  • Inga Hänelt

    (Goethe University Frankfurt)

Abstract

K+ homeostasis is crucial for bacterial survival. The bacterial K+ channel KtrAB is regulated by the binding of ADP and ATP to the cytosolic RCK subunits KtrA. While the ligand-induced conformational changes in KtrA are well described, the transmission to the gating regions within KtrB is not understood. Here, we present a cryo-EM structure of the ADP-bound, inactive KtrAB complex from Vibrio alginolyticus, which resolves part of KtrB’s N termini. They are short intrinsically disordered regions (IDRs) located at the interface of KtrA and KtrB. We reveal that these IDRs play a decisive role in ATP-mediated channel opening, while the closed ADP-bound state does not depend on the N-termini. We propose an allosteric mechanism, in which ATP-induced conformational changes within KtrA trigger an interaction of KtrB’s N-terminal IDRs with the membrane, stabilizing the active and conductive state of KtrAB.

Suggested Citation

  • Janina Stautz & David Griwatz & Susann Kaltwasser & Ahmad Reza Mehdipour & Sophie Ketter & Celina Thiel & Dorith Wunnicke & Marina Schrecker & Deryck J. Mills & Gerhard Hummer & Janet Vonck & Inga Hän, 2025. "A short intrinsically disordered region at KtrB’s N-terminus facilitates allosteric regulation of K+ channel KtrAB," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59546-z
    DOI: 10.1038/s41467-025-59546-z
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    1. Wesley Tien Chiang & Yao-Kai Chang & Wei-Han Hui & Shu-Wei Chang & Chen-Yi Liao & Yi-Chuan Chang & Chun-Jung Chen & Wei-Chen Wang & Chien-Chen Lai & Chun-Hsiung Wang & Siou-Ying Luo & Ya-Ping Huang & , 2024. "Structural basis and synergism of ATP and Na+ activation in bacterial K+ uptake system KtrAB," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Youxing Jiang & Alice Lee & Jiayun Chen & Martine Cadene & Brian T. Chait & Roderick MacKinnon, 2002. "The open pore conformation of potassium channels," Nature, Nature, vol. 417(6888), pages 523-526, May.
    3. Yu Cao & Yaping Pan & Hua Huang & Xiangshu Jin & Elena J. Levin & Brian Kloss & Ming Zhou, 2013. "Gating of the TrkH ion channel by its associated RCK protein TrkA," Nature, Nature, vol. 496(7445), pages 317-322, April.
    4. Benedikt Goretzki & Christoph Wiedemann & Brett A. McCray & Stefan L. Schäfer & Jasmin Jansen & Frederike Tebbe & Sarah-Ana Mitrovic & Julia Nöth & Ainara Claveras Cabezudo & Jack K. Donohue & Cy M. J, 2023. "Crosstalk between regulatory elements in disordered TRPV4 N-terminus modulates lipid-dependent channel activity," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    5. Arthur Prindle & Jintao Liu & Munehiro Asally & San Ly & Jordi Garcia-Ojalvo & Gürol M. Süel, 2015. "Ion channels enable electrical communication in bacterial communities," Nature, Nature, vol. 527(7576), pages 59-63, November.
    6. Chen Fan & Nattakan Sukomon & Emelie Flood & Jan Rheinberger & Toby W. Allen & Crina M. Nimigean, 2020. "Ball-and-chain inactivation in a calcium-gated potassium channel," Nature, Nature, vol. 580(7802), pages 288-293, April.
    7. Ricardo S. Vieira-Pires & Andras Szollosi & João H. Morais-Cabral, 2013. "The structure of the KtrAB potassium transporter," Nature, Nature, vol. 496(7445), pages 323-328, April.
    8. Hanzhi Zhang & Yaping Pan & Liya Hu & M. Ashley Hudson & Katrina S. Hofstetter & Zhichun Xu & Mingqiang Rong & Zhao Wang & B. V. Venkataram Prasad & Steve W. Lockless & Wah Chiu & Ming Zhou, 2020. "TrkA undergoes a tetramer-to-dimer conversion to open TrkH which enables changes in membrane potential," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    9. Yu Cao & Xiangshu Jin & Hua Huang & Mehabaw Getahun Derebe & Elena J. Levin & Venkataraman Kabaleeswaran & Yaping Pan & Marco Punta & James Love & Jun Weng & Matthias Quick & Sheng Ye & Brian Kloss & , 2011. "Crystal structure of a potassium ion transporter, TrkH," Nature, Nature, vol. 471(7338), pages 336-340, March.
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