Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 119, Issue 26, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2200364119
Keywords
voltage-sensing phosphatase; voltage sensor domain; hydrophobicity; Anap; phosphoinositide
Categories
Funding
- Honjo International Scholarship Foundation
- Ministry of Education, Culture, Sports, Science and Technology [JP15H05901, JP20H05791]
- Japan Society for the Promotion of Science, KAKENHI [JP19K06585, JP19H03401, JP21H02444]
- Japan Science and Technology Agency, CREST [JPMJCR14M3]
- Mitsubishi Foundation
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This study investigated the electrochemical coupling in Ciona intestinalis VSP using electrophysiology, fluorometry, and structural modeling. It was found that two hydrophobic residues at the bottom of S4 play a crucial role in the VSD-CCR coupling, with the hydrophobic spine acting as a central hub for translating electrical signals into chemical signals in VSP.
Voltage-sensing phosphatase (VSP) consists of a voltage sensor domain (VSD) and a cytoplasmic catalytic region (CCR), which is similar to phosphatase and tensin homolog (PTEN). How the VSD regulates the innate enzyme component of VSP remains unclear. Here, we took a combined approach that entailed the use of electrophysiology, fluorometry, and structural modeling to study the electrochemical coupling in Ciona intestinalis VSP. We found that two hydrophobic residues at the lowest part of S4 play an essential role in the later transition of VSD-CCR coupling. Voltage clamp fluorometry and disulfide bond locking indicated that S4 and its neighboring linker move as one helix (S4-linker helix) and approach the hydrophobic spine in the CCR, a structure located near the cell membrane and also conserved in PTEN. We propose that the hydrophobic spine operates as a hub for translating an electrical signal into a chemical one in VSP.
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