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Coupling sensor to enzyme in the voltage sensing phosphatase

Author

Listed:
  • Yawei Yu

    (University of California)

  • Lin Zhang

    (University of California)

  • Baobin Li

    (University of California
    Fudan University)

  • Zhu Fu

    (University of California)

  • Stephen G. Brohawn

    (University of California
    University of California
    University of California)

  • Ehud Y. Isacoff

    (University of California
    University of California
    University of California
    Lawrence Berkeley National Laboratory)

Abstract

Voltage-sensing phosphatases (VSPs) dephosphorylate phosphoinositide (PIP) signaling lipids in response to membrane depolarization. VSPs possess an S4-containing voltage sensor domain (VSD), resembling that of voltage-gated cation channels, and a lipid phosphatase domain (PD). The mechanism by which voltage turns on enzyme activity is unclear. Structural analysis and modeling suggest several sites of VSD-PD interaction that could couple voltage sensing to catalysis. Voltage clamp fluorometry reveals voltage-driven rearrangements in three sites implicated earlier in enzyme activation—the VSD-PD linker, gating loop and R loop—as well as the N-terminal domain, which has not yet been explored. N-terminus mutations perturb both rearrangements in the other segments and enzyme activity. Our results provide a model for a dynamic assembly by which S4 controls the catalytic site.

Suggested Citation

  • Yawei Yu & Lin Zhang & Baobin Li & Zhu Fu & Stephen G. Brohawn & Ehud Y. Isacoff, 2024. "Coupling sensor to enzyme in the voltage sensing phosphatase," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50319-8
    DOI: 10.1038/s41467-024-50319-8
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