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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
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    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.
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