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TrkA undergoes a tetramer-to-dimer conversion to open TrkH which enables changes in membrane potential

Author

Listed:
  • Hanzhi Zhang

    (Baylor College of Medicine)

  • Yaping Pan

    (Baylor College of Medicine)

  • Liya Hu

    (Baylor College of Medicine)

  • M. Ashley Hudson

    (Texas A&M University)

  • Katrina S. Hofstetter

    (Texas A&M University)

  • Zhichun Xu

    (Baylor College of Medicine)

  • Mingqiang Rong

    (Baylor College of Medicine)

  • Zhao Wang

    (Baylor College of Medicine
    Baylor College of Medicine)

  • B. V. Venkataram Prasad

    (Baylor College of Medicine)

  • Steve W. Lockless

    (Texas A&M University)

  • Wah Chiu

    (Stanford University)

  • Ming Zhou

    (Baylor College of Medicine)

Abstract

TrkH is a bacterial ion channel implicated in K+ uptake and pH regulation. TrkH assembles with its regulatory protein, TrkA, which closes the channel when bound to ADP and opens it when bound to ATP. However, it is unknown how nucleotides control the gating of TrkH through TrkA. Here we report the structures of the TrkH-TrkA complex in the presence of ADP or ATP. TrkA forms a tetrameric ring when bound to ADP and constrains TrkH to a closed conformation. The TrkA ring splits into two TrkA dimers in the presence of ATP and releases the constraints on TrkH, resulting in an open channel conformation. Functional studies show that both the tetramer-to-dimer conversion of TrkA and the loss of constraints on TrkH are required for channel gating. In addition, deletion of TrkA in Escherichia coli depolarizes the cell, suggesting that the TrkH-TrkA complex couples changes in intracellular nucleotides to membrane potential.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14240-9
    DOI: 10.1038/s41467-019-14240-9
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