IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39388-3.html
   My bibliography  Save this article

Structure of human CALHM1 reveals key locations for channel regulation and blockade by ruthenium red

Author

Listed:
  • Johanna L. Syrjänen

    (Cold Spring Harbor Laboratory, Cold Spring Harbor)

  • Max Epstein

    (Cold Spring Harbor Laboratory, Cold Spring Harbor)

  • Ricardo Gómez

    (Cold Spring Harbor Laboratory, Cold Spring Harbor)

  • Hiro Furukawa

    (Cold Spring Harbor Laboratory, Cold Spring Harbor)

Abstract

Calcium homeostasis modulator 1 (CALHM1) is a voltage-dependent channel involved in neuromodulation and gustatory signaling. Despite recent progress in the structural biology of CALHM1, insights into functional regulation, pore architecture, and channel blockade remain limited. Here we present the cryo-EM structure of human CALHM1, revealing an octameric assembly pattern similar to the non-mammalian CALHM1s and the lipid-binding pocket conserved across species. We demonstrate by MD simulations that this pocket preferentially binds a phospholipid over cholesterol to stabilize its structure and regulate the channel activities. Finally, we show that residues in the amino-terminal helix form the channel pore that ruthenium red binds and blocks.

Suggested Citation

  • Johanna L. Syrjänen & Max Epstein & Ricardo Gómez & Hiro Furukawa, 2023. "Structure of human CALHM1 reveals key locations for channel regulation and blockade by ruthenium red," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39388-3
    DOI: 10.1038/s41467-023-39388-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39388-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-39388-3?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. Kei Saotome & Swetha E. Murthy & Jennifer M. Kefauver & Tess Whitwam & Ardem Patapoutian & Andrew B. Ward, 2018. "Structure of the mechanically activated ion channel Piezo1," Nature, Nature, vol. 554(7693), pages 481-486, February.
    2. Wooyoung Choi & Nicolina Clemente & Weinan Sun & Juan Du & Wei Lü, 2019. "The structures and gating mechanism of human calcium homeostasis modulator 2," Nature, Nature, vol. 576(7785), pages 163-167, December.
    3. Akiyuki Taruno & Valérie Vingtdeux & Makoto Ohmoto & Zhongming Ma & Gennady Dvoryanchikov & Ang Li & Leslie Adrien & Haitian Zhao & Sze Leung & Maria Abernethy & Jeremy Koppel & Peter Davies & Mortime, 2013. "CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes," Nature, Nature, vol. 495(7440), pages 223-226, March.
    4. Arthur Neuberger & Kirill D. Nadezhdin & Alexander I. Sobolevsky, 2021. "Structural mechanisms of TRPV6 inhibition by ruthenium red and econazole," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    Full references (including those not matched with items on IDEAS)

    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.

    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. Arthur Neuberger & Yury A. Trofimov & Maria V. Yelshanskaya & Kirill D. Nadezhdin & Nikolay A. Krylov & Roman G. Efremov & Alexander I. Sobolevsky, 2023. "Structural mechanism of human oncochannel TRPV6 inhibition by the natural phytoestrogen genistein," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Shilong Yang & Xinwen Miao & Steven Arnold & Boxuan Li & Alan T. Ly & Huan Wang & Matthew Wang & Xiangfu Guo & Medha M. Pathak & Wenting Zhao & Charles D. Cox & Zheng Shi, 2022. "Membrane curvature governs the distribution of Piezo1 in live cells," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Xin-yu He & Xiao Fan & Lei Qu & Xiang Wang & Li Jiang & Ling-jie Sang & Cheng-yu Shi & Siyi Lin & Jie-cheng Yang & Zuo-zhen Yang & Kai Lei & Jun-hong Li & Huai-qiang Ju & Qingfeng Yan & Jian Liu & Fud, 2023. "LncRNA modulates Hippo-YAP signaling to reprogram iron metabolism," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Nathalia G. Amado & Elena D. Nosyreva & David Thompson & Thomas J. Egeland & Osita W. Ogujiofor & Michelle Yang & Alexandria N. Fusco & Niccolo Passoni & Jeremy Mathews & Brandi Cantarel & Linda A. Ba, 2024. "PIEZO1 loss-of-function compound heterozygous mutations in the rare congenital human disorder Prune Belly Syndrome," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    5. Arthur Neuberger & Kirill D. Nadezhdin & Alexander I. Sobolevsky, 2021. "Structural mechanisms of TRPV6 inhibition by ruthenium red and econazole," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    6. 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.
    7. T. Bertie Ansell & Wanling Song & Claire E. Coupland & Loic Carrique & Robin A. Corey & Anna L. Duncan & C. Keith Cassidy & Maxwell M. G. Geurts & Tim Rasmussen & Andrew B. Ward & Christian Siebold & , 2023. "LipIDens: simulation assisted interpretation of lipid densities in cryo-EM structures of membrane proteins," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    8. Francisco Andrés Peralta & Mélaine Balcon & Adeline Martz & Deniza Biljali & Federico Cevoli & Benoit Arnould & Antoine Taly & Thierry Chataigneau & Thomas Grutter, 2023. "Optical control of PIEZO1 channels," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    9. Junping Fan & Han Ke & Jing Lei & Jin Wang & Makoto Tominaga & Xiaoguang Lei, 2024. "Structural basis of TRPV1 inhibition by SAF312 and cholesterol," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    10. 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.
    11. Arthur Neuberger & Yury A. Trofimov & Maria V. Yelshanskaya & Jeffrey Khau & Kirill D. Nadezhdin & Lena S. Khosrof & Nikolay A. Krylov & Roman G. Efremov & Alexander I. Sobolevsky, 2023. "Molecular pathway and structural mechanism of human oncochannel TRPV6 inhibition by the phytocannabinoid tetrahydrocannabivarin," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    12. Jonathan Mount & Grigory Maksaev & Brock T. Summers & James A. J. Fitzpatrick & Peng Yuan, 2022. "Structural basis for mechanotransduction in a potassium-dependent mechanosensitive ion channel," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    13. Amandeep Kaur & Madhu & Alok Sharma & Kashmir Singh & Santosh Kumar Upadhyay, 2023. "Exploration of Piezo Channels in Bread Wheat ( Triticum aestivum L.)," Agriculture, MDPI, vol. 13(4), pages 1-16, March.
    14. Kirill D. Nadezhdin & Irina A. Talyzina & Aravind Parthasarathy & Arthur Neuberger & David X. Zhang & Alexander I. Sobolevsky, 2023. "Structure of human TRPV4 in complex with GTPase RhoA," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    15. Kenjiro Yoshimura & Kazuko Iida & Hidetoshi Iida, 2021. "MCAs in Arabidopsis are Ca2+-permeable mechanosensitive channels inherently sensitive to membrane tension," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    16. Arthur Neuberger & Mai Oda & Yury A. Nikolaev & Kirill D. Nadezhdin & Elena O. Gracheva & Sviatoslav N. Bagriantsev & Alexander I. Sobolevsky, 2023. "Human TRPV1 structure and inhibition by the analgesic SB-366791," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    17. Liying Zhang & Charlotte Simonsen & Lucie Zimova & Kaituo Wang & Lavanya Moparthi & Rachelle Gaudet & Maria Ekoff & Gunnar Nilsson & Ute A. Hellmich & Viktorie Vlachova & Pontus Gourdon & Peter M. Zyg, 2022. "Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    18. Jingying Zhang & Grigory Maksaev & Peng Yuan, 2023. "Open structure and gating of the Arabidopsis mechanosensitive ion channel MSL10," Nature Communications, Nature, vol. 14(1), pages 1-9, 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_s41467-023-39388-3. 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.