IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v558y2018i7709d10.1038_s41586-018-0134-y.html
   My bibliography  Save this article

Structure of a volume-regulated anion channel of the LRRC8 family

Author

Listed:
  • Dawid Deneka

    (University of Zurich)

  • Marta Sawicka

    (University of Zurich)

  • Andy K. M. Lam

    (University of Zurich)

  • Cristina Paulino

    (University of Zurich
    Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen)

  • Raimund Dutzler

    (University of Zurich)

Abstract

Volume-regulated anion channels are activated in response to hypotonic stress. These channels are composed of closely related paralogues of the leucine-rich repeat-containing protein 8 (LRRC8) family that co-assemble to form hexameric complexes. Here, using cryo-electron microscopy and X-ray crystallography, we determine the structure of a homomeric channel of the obligatory subunit LRRC8A. This protein conducts ions and has properties in common with endogenous heteromeric channels. Its modular structure consists of a transmembrane pore domain followed by a cytoplasmic leucine-rich repeat domain. The transmembrane domain, which is structurally related to connexin proteins, is wide towards the cytoplasm but constricted on the outside by a structural unit that acts as a selectivity filter. An excess of basic residues in the filter and throughout the pore attracts anions by electrostatic interaction. Our work reveals the previously unknown architecture of volume-regulated anion channels and their mechanism of selective anion conduction.

Suggested Citation

  • Dawid Deneka & Marta Sawicka & Andy K. M. Lam & Cristina Paulino & Raimund Dutzler, 2018. "Structure of a volume-regulated anion channel of the LRRC8 family," Nature, Nature, vol. 558(7709), pages 254-259, June.
    • Handle: RePEc:nat:nature:v:558:y:2018:i:7709:d:10.1038_s41586-018-0134-y
    DOI: 10.1038/s41586-018-0134-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-018-0134-y
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/s41586-018-0134-y?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Nazia Hussain & Ashish Apotikar & Shabareesh Pidathala & Sourajit Mukherjee & Ananth Prasad Burada & Sujit Kumar Sikdar & Kutti R. Vinothkumar & Aravind Penmatsa, 2024. "Cryo-EM structures of pannexin 1 and 3 reveal differences among pannexin isoforms," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Zhihui He & Yonghui Zhao & Michael J. Rau & James A. J. Fitzpatrick & Rajan Sah & Hongzhen Hu & Peng Yuan, 2023. "Structural and functional analysis of human pannexin 2 channel," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    3. Hang Zhang & Shiyu Wang & Zhenzhen Zhang & Mengzhuo Hou & Chunyu Du & Zhenye Zhao & Horst Vogel & Zhifang Li & Kaige Yan & Xiaokang Zhang & Jianping Lu & Yujie Liang & Shuguang Yuan & Daping Wang & Hu, 2023. "Cryo-EM structure of human heptameric pannexin 2 channel," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    4. Yuman Wang & Zaiqiao Sun & Jieming Ping & Jianlong Tang & Boxiao He & Teding Chang & Qian Zhou & Shijie Yuan & Zhaohui Tang & Xin Li & Yan Lu & Ran He & Ximiao He & Zheng Liu & Lei Yin & Ning Wu, 2023. "Cell volume controlled by LRRC8A-formed volume-regulated anion channels fine-tunes T cell activation and function," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Susheel K. Gunasekar & Litao Xie & Ashutosh Kumar & Juan Hong & Pratik R. Chheda & Chen Kang & David M. Kern & Chau My-Ta & Joshua Maurer & John Heebink & Eva E. Gerber & Wojciech J. Grzesik & Macaula, 2022. "Small molecule SWELL1 complex induction improves glycemic control and nonalcoholic fatty liver disease in murine Type 2 diabetes," Nature Communications, Nature, vol. 13(1), pages 1-25, 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:nature:v:558:y:2018:i:7709:d:10.1038_s41586-018-0134-y. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.