IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-42489-8.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-42489-8
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-42489-8?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. 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.
    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. Haon Futamata & Masahiro Fukuda & Rie Umeda & Keitaro Yamashita & Atsuhiro Tomita & Satoe Takahashi & Takafumi Shikakura & Shigehiko Hayashi & Tsukasa Kusakizako & Tomohiro Nishizawa & Kazuaki Homma &, 2022. "Cryo-EM structures of thermostabilized prestin provide mechanistic insights underlying outer hair cell electromotility," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Sepehr Dehghani-Ghahnaviyeh & Zhiyu Zhao & Emad Tajkhorshid, 2022. "Lipid-mediated prestin organization in outer hair cell membranes and its implications in sound amplification," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Lie Wang & Anthony Hoang & Eva Gil-Iturbe & Arthur Laganowsky & Matthias Quick & Ming Zhou, 2024. "Mechanism of anion exchange and small-molecule inhibition of pendrin," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    4. Benedikt T. Kuhn & Jonathan Zöller & Iwan Zimmermann & Tim Gemeinhardt & Dogukan H. Özkul & Julian D. Langer & Markus A. Seeger & Eric R. Geertsma, 2024. "Interdomain-linkers control conformational transitions in the SLC23 elevator transporter UraA," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    5. Wenxin Hu & Alex Song & Hongjin Zheng, 2024. "Substrate binding plasticity revealed by Cryo-EM structures of SLC26A2," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    6. Mingxing Wang & Jin He & Shanshan Li & Qianwen Cai & Kaiming Zhang & Ji She, 2023. "Structural basis of vitamin C recognition and transport by mammalian SVCT1 transporter," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
    7. 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.
    8. Mingfeng Zhang & Yuanyue Shan & Charles D. Cox & Duanqing Pei, 2023. "A mechanical-coupling mechanism in OSCA/TMEM63 channel mechanosensitivity," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    9. Adam Sheppard & Massimo Ralli & Antonio Gilardi & Richard Salvi, 2020. "Occupational Noise: Auditory and Non-Auditory Consequences," IJERPH, MDPI, vol. 17(23), pages 1-15, December.
    10. Yuanyue Shan & Mengmeng Zhang & Meiyu Chen & Xinyi Guo & Ying Li & Mingfeng Zhang & Duanqing Pei, 2024. "Activation mechanisms of dimeric mechanosensitive OSCA/TMEM63 channels," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    11. Lie Wang & Ming Zhou, 2023. "Structure of a eukaryotic cholinephosphotransferase-1 reveals mechanisms of substrate recognition and catalysis," Nature Communications, Nature, vol. 14(1), pages 1-8, 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_s41467-023-42489-8. 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.