IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-45514-6.html
   My bibliography  Save this article

Dynamics of activation in the voltage-sensing domain of Ciona intestinalis phosphatase Ci-VSP

Author

Listed:
  • Spencer C. Guo

    (The University of Chicago
    The University of Chicago)

  • Rong Shen

    (The University of Chicago)

  • Benoît Roux

    (The University of Chicago
    The University of Chicago
    The University of Chicago)

  • Aaron R. Dinner

    (The University of Chicago
    The University of Chicago
    The University of Chicago)

Abstract

The Ciona intestinalis voltage-sensing phosphatase (Ci-VSP) is a membrane protein containing a voltage-sensing domain (VSD) that is homologous to VSDs from voltage-gated ion channels responsible for cellular excitability. Previously published crystal structures of Ci-VSD in putative resting and active conformations suggested a helical-screw voltage sensing mechanism in which the S4 helix translocates and rotates to enable exchange of salt-bridge partners, but the microscopic details of the transition between the resting and active conformations remained unknown. Here, by combining extensive molecular dynamics simulations with a recently developed computational framework based on dynamical operators, we elucidate the microscopic mechanism of the resting-active transition at physiological membrane potential. Sparse regression reveals a small set of coordinates that distinguish intermediates that are hidden from electrophysiological measurements. The intermediates arise from a noncanonical helical-screw mechanism in which translocation, rotation, and side-chain movement of the S4 helix are only loosely coupled. These results provide insights into existing experimental and computational findings on voltage sensing and suggest ways of further probing its mechanism.

Suggested Citation

  • Spencer C. Guo & Rong Shen & Benoît Roux & Aaron R. Dinner, 2024. "Dynamics of activation in the voltage-sensing domain of Ciona intestinalis phosphatase Ci-VSP," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45514-6
    DOI: 10.1038/s41467-024-45514-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-45514-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-45514-6?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. Boris Musset & Susan M. E. Smith & Sindhu Rajan & Deri Morgan & Vladimir V. Cherny & Thomas E. DeCoursey, 2011. "Aspartate 112 is the selectivity filter of the human voltage-gated proton channel," Nature, Nature, vol. 480(7376), pages 273-277, December.
    2. Youxing Jiang & Alice Lee & Jiayun Chen & Vanessa Ruta & Martine Cadene & Brian T. Chait & Roderick MacKinnon, 2003. "X-ray structure of a voltage-dependent K+ channel," Nature, Nature, vol. 423(6935), pages 33-41, May.
    3. Daniel Schmidt & Qiu-Xing Jiang & Roderick MacKinnon, 2006. "Phospholipids and the origin of cationic gating charges in voltage sensors," Nature, Nature, vol. 444(7120), pages 775-779, December.
    4. Yoshimichi Murata & Hirohide Iwasaki & Mari Sasaki & Kazuo Inaba & Yasushi Okamura, 2005. "Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor," Nature, Nature, vol. 435(7046), pages 1239-1243, June.
    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. Ozer, Mahmut, 2005. "Determination of rate kinetics in ion channels by the path probability method and Onsager reciprocity theorem," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 357(3), pages 397-414.
    2. Turkan Haliloglu & Nir Ben-Tal, 2008. "Cooperative Transition between Open and Closed Conformations in Potassium Channels," PLOS Computational Biology, Public Library of Science, vol. 4(8), pages 1-11, August.
    3. Tobias Linder & Bert L de Groot & Anna Stary-Weinzinger, 2013. "Probing the Energy Landscape of Activation Gating of the Bacterial Potassium Channel KcsA," PLOS Computational Biology, Public Library of Science, vol. 9(5), pages 1-9, May.
    4. Shrivastava, Rajan & Malik, Chetan & Ghosh, Subhendu, 2016. "Open channel current noise analysis of S6 peptides from KvAP channel on bilayer lipid membrane shows bimodal power law scaling," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 451(C), pages 533-540.
    5. Bryan Cernuda & Christopher Thomas Fernandes & Salma Mohamed Allam & Matthew Orzillo & Gabrielle Suppa & Zuleen Chia Chang & Demosthenes Athanasopoulos & Zafir Buraei, 2019. "The molecular determinants of R-roscovitine block of hERG channels," PLOS ONE, Public Library of Science, vol. 14(9), pages 1-26, September.
    6. Jin Wang & Zeyuan Song & Miaolu He & Yongchao Qian & Di Wang & Zheng Cui & Yuan Feng & Shangzhen Li & Bo Huang & Xiangyu Kong & Jinming Han & Lei Wang, 2024. "Light-responsive and ultrapermeable two-dimensional metal-organic framework membrane for efficient ionic energy harvesting," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    7. Georg Kuenze & Amanda M Duran & Hope Woods & Kathryn R Brewer & Eli Fritz McDonald & Carlos G Vanoye & Alfred L George Jr. & Charles R Sanders & Jens Meiler, 2019. "Upgraded molecular models of the human KCNQ1 potassium channel," PLOS ONE, Public Library of Science, vol. 14(9), pages 1-33, September.
    8. Chang Zhao & Parker D. Webster & Alexis Angeli & Francesco Tombola, 2023. "Mechanically-primed voltage-gated proton channels from angiosperm plants," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    9. 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:15:y:2024:i:1:d:10.1038_s41467-024-45514-6. 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.