IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-48057-y.html
   My bibliography  Save this article

Structural basis and synergism of ATP and Na+ activation in bacterial K+ uptake system KtrAB

Author

Listed:
  • Wesley Tien Chiang

    (National Chung Hsing University)

  • Yao-Kai Chang

    (Academia Sinica)

  • Wei-Han Hui

    (National Taiwan University)

  • Shu-Wei Chang

    (National Taiwan University
    National Taiwan University)

  • Chen-Yi Liao

    (National Chung Hsing University)

  • Yi-Chuan Chang

    (National Chung Hsing University)

  • Chun-Jung Chen

    (National Synchrotron Radiation Research Center)

  • Wei-Chen Wang

    (National Chung Hsing University)

  • Chien-Chen Lai

    (National Chung Hsing University
    China Medical University)

  • Chun-Hsiung Wang

    (Academia Sinica)

  • Siou-Ying Luo

    (Academia Sinica)

  • Ya-Ping Huang

    (Academia Sinica)

  • Shan-Ho Chou

    (National Chung Hsing University)

  • Tzyy-Leng Horng

    (Feng Chia University)

  • Ming-Hon Hou

    (National Chung Hsing University)

  • Stephen P. Muench

    (University of Leeds)

  • Ren-Shiang Chen

    (Tunghai University)

  • Ming-Daw Tsai

    (Academia Sinica
    National Taiwan University)

  • Nien-Jen Hu

    (National Chung Hsing University
    National Chung Hsing University)

Abstract

The K+ uptake system KtrAB is essential for bacterial survival in low K+ environments. The activity of KtrAB is regulated by nucleotides and Na+. Previous studies proposed a putative gating mechanism of KtrB regulated by KtrA upon binding to ATP or ADP. However, how Na+ activates KtrAB and the Na+ binding site remain unknown. Here we present the cryo-EM structures of ATP- and ADP-bound KtrAB from Bacillus subtilis (BsKtrAB) both solved at 2.8 Å. A cryo-EM density at the intra-dimer interface of ATP-KtrA was identified as Na+, as supported by X-ray crystallography and ICP-MS. Thermostability assays and functional studies demonstrated that Na+ binding stabilizes the ATP-bound BsKtrAB complex and enhances its K+ flux activity. Comparing ATP- and ADP-BsKtrAB structures suggests that BsKtrB Arg417 and Phe91 serve as a channel gate. The synergism of ATP and Na+ in activating BsKtrAB is likely applicable to Na+-activated K+ channels in central nervous system.

Suggested Citation

  • Wesley Tien Chiang & Yao-Kai Chang & Wei-Han Hui & Shu-Wei Chang & Chen-Yi Liao & Yi-Chuan Chang & Chun-Jung Chen & Wei-Chen Wang & Chien-Chen Lai & Chun-Hsiung Wang & Siou-Ying Luo & Ya-Ping Huang & , 2024. "Structural basis and synergism of ATP and Na+ activation in bacterial K+ uptake system KtrAB," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48057-y
    DOI: 10.1038/s41467-024-48057-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-48057-y
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-48057-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
    ---><---

    References listed on IDEAS

    as
    1. Olga Boudker & Renae M. Ryan & Dinesh Yernool & Keiko Shimamoto & Eric Gouaux, 2007. "Coupling substrate and ion binding to extracellular gate of a sodium-dependent aspartate transporter," Nature, Nature, vol. 445(7126), pages 387-393, January.
    2. Frank J. Smith & Victor P.T. Pau & Gino Cingolani & Brad S. Rothberg, 2013. "Structural basis of allosteric interactions among Ca2+-binding sites in a K+ channel RCK domain," Nature Communications, Nature, vol. 4(1), pages 1-10, December.
    3. Yu Cao & Yaping Pan & Hua Huang & Xiangshu Jin & Elena J. Levin & Brian Kloss & Ming Zhou, 2013. "Gating of the TrkH ion channel by its associated RCK protein TrkA," Nature, Nature, vol. 496(7445), pages 317-322, April.
    4. Ricardo S. Vieira-Pires & Andras Szollosi & João H. Morais-Cabral, 2013. "The structure of the KtrAB potassium transporter," Nature, Nature, vol. 496(7445), pages 323-328, April.
    5. Hanzhi Zhang & Yaping Pan & Liya Hu & M. Ashley Hudson & Katrina S. Hofstetter & Zhichun Xu & Mingqiang Rong & Zhao Wang & B. V. Venkataram Prasad & Steve W. Lockless & Wah Chiu & Ming Zhou, 2020. "TrkA undergoes a tetramer-to-dimer conversion to open TrkH which enables changes in membrane potential," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    6. Yu Cao & Xiangshu Jin & Hua Huang & Mehabaw Getahun Derebe & Elena J. Levin & Venkataraman Kabaleeswaran & Yaping Pan & Marco Punta & James Love & Jun Weng & Matthias Quick & Sheng Ye & Brian Kloss & , 2011. "Crystal structure of a potassium ion transporter, TrkH," Nature, Nature, vol. 471(7338), pages 336-340, March.
    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. Ashutosh Gulati & Surabhi Kokane & Annemarie Perez-Boerema & Claudia Alleva & Pascal F. Meier & Rei Matsuoka & David Drew, 2024. "Structure and mechanism of the K+/H+ exchanger KefC," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. 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.
    3. Michał Uflewski & Tobias Rindfleisch & Kübra Korkmaz & Enrico Tietz & Sarah Mielke & Viviana Correa Galvis & Beatrix Dünschede & Marcin Luzarowski & Aleksandra Skirycz & Markus Schwarzländer & Deserah, 2024. "The thylakoid proton antiporter KEA3 regulates photosynthesis in response to the chloroplast energy status," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    4. Emanuela Colucci & Zaid R. Anshari & Miyer F. Patiño-Ruiz & Mariia Nemchinova & Jacob Whittaker & Dirk J. Slotboom & Albert Guskov, 2023. "Mutation in glutamate transporter homologue GltTk provides insights into pathologic mechanism of episodic ataxia 6," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    5. Biao Qiu & Olga Boudker, 2023. "Symport and antiport mechanisms of human glutamate transporters," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    6. Anna M. Borowska & Maria Gabriella Chiariello & Alisa A. Garaeva & Jan Rheinberger & Siewert J. Marrink & Cristina Paulino & Dirk J. Slotboom, 2024. "Structural basis of the obligatory exchange mode of human neutral amino acid transporter ASCT2," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    7. Takafumi Kato & Tsukasa Kusakizako & Chunhuan Jin & Xinyu Zhou & Ryuichi Ohgaki & LiLi Quan & Minhui Xu & Suguru Okuda & Kan Kobayashi & Keitaro Yamashita & Tomohiro Nishizawa & Yoshikatsu Kanai & Osa, 2022. "Structural insights into inhibitory mechanism of human excitatory amino acid transporter EAAT2," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    8. David B. Sauer & Jennifer J. Marden & Joseph C. Sudar & Jinmei Song & Christopher Mulligan & Da-Neng Wang, 2022. "Structural basis of ion – substrate coupling in the Na+-dependent dicarboxylate transporter VcINDY," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    9. Zhenglai Zhang & Huiwen Chen & Ze Geng & Zhuoya Yu & Hang Li & Yanli Dong & Hongwei Zhang & Zhuo Huang & Juquan Jiang & Yan Zhao, 2022. "Structural basis of ligand binding modes of human EAAT2," Nature Communications, Nature, vol. 13(1), pages 1-10, 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_s41467-024-48057-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.

    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.