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Elevator-like movements of prestin mediate outer hair cell electromotility

Author

Listed:
  • Makoto F. Kuwabara

    (Philipps University Marburg)

  • Bassam G. Haddad

    (Forschungszentrum Jülich)

  • Dominik Lenz-Schwab

    (Philipps University Marburg)

  • Julia Hartmann

    (Philipps University Marburg)

  • Piersilvio Longo

    (Forschungszentrum Jülich)

  • Britt-Marie Huckschlag

    (Philipps University Marburg)

  • Anneke Fuß

    (Philipps University Marburg)

  • Annalisa Questino

    (Philipps University Marburg)

  • Thomas K. Berger

    (Philipps University Marburg)

  • Jan-Philipp Machtens

    (Forschungszentrum Jülich
    RWTH Aachen University)

  • Dominik Oliver

    (Philipps University Marburg
    Philipps University
    Universities of Marburg and Giessen)

Abstract

The outstanding acuity of the mammalian ear relies on cochlear amplification, an active mechanism based on the electromotility (eM) of outer hair cells. eM is a piezoelectric mechanism generated by little-understood, voltage-induced conformational changes of the anion transporter homolog prestin (SLC26A5). We used a combination of molecular dynamics (MD) simulations and biophysical approaches to identify the structural dynamics of prestin that mediate eM. MD simulations showed that prestin samples a vast conformational landscape with expanded (ES) and compact (CS) states beyond previously reported prestin structures. Transition from CS to ES is dominated by the translational-rotational movement of prestin’s transport domain, akin to elevator-type substrate translocation by related solute carriers. Reversible transition between CS and ES states was supported experimentally by cysteine accessibility scanning, cysteine cross-linking between transport and scaffold domains, and voltage-clamp fluorometry (VCF). Our data demonstrate that prestin’s piezoelectric dynamics recapitulate essential steps of a structurally conserved ion transport cycle.

Suggested Citation

  • Makoto F. Kuwabara & Bassam G. Haddad & Dominik Lenz-Schwab & Julia Hartmann & Piersilvio Longo & Britt-Marie Huckschlag & Anneke Fuß & Annalisa Questino & Thomas K. Berger & Jan-Philipp Machtens & Do, 2023. "Elevator-like movements of prestin mediate outer hair cell electromotility," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42489-8
    DOI: 10.1038/s41467-023-42489-8
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    References listed on IDEAS

    as
    1. Qianying Liu & Xiang Zhang & Hui Huang & Yuxin Chen & Fang Wang & Aihua Hao & Wuqiang Zhan & Qiyu Mao & Yuxia Hu & Lin Han & Yifang Sun & Meng Zhang & Zhimin Liu & Geng-Lin Li & Weijia Zhang & Yilai S, 2023. "Asymmetric pendrin homodimer reveals its molecular mechanism as anion exchanger," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    2. Jing Zheng & Weixing Shen & David Z. Z. He & Kevin B. Long & Laird D. Madison & Peter Dallos, 2000. "Prestin is the motor protein of cochlear outer hair cells," Nature, Nature, vol. 405(6783), pages 149-155, May.
    3. Dmitry Gorbunov & Mattia Sturlese & Florian Nies & Murielle Kluge & Massimo Bellanda & Roberto Battistutta & Dominik Oliver, 2014. "Molecular architecture and the structural basis for anion interaction in prestin and SLC26 transporters," Nature Communications, Nature, vol. 5(1), pages 1-13, May.
    4. Navid Bavi & Michael David Clark & Gustavo F. Contreras & Rong Shen & Bharat G. Reddy & Wieslawa Milewski & Eduardo Perozo, 2021. "The conformational cycle of prestin underlies outer-hair cell electromotility," Nature, Nature, vol. 600(7889), pages 553-558, December.
    5. Lie Wang & Kehan Chen & Ming Zhou, 2021. "Structure and function of an Arabidopsis thaliana sulfate transporter," Nature Communications, Nature, vol. 12(1), pages 1-8, December.
    6. M. Charles Liberman & Jiangang Gao & David Z. Z. He & Xudong Wu & Shuping Jia & Jian Zuo, 2002. "Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier," Nature, Nature, vol. 419(6904), pages 300-304, September.
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