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Interaction between S4 and the phosphatase domain mediates electrochemical coupling in voltage-sensing phosphatase (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 t...

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Autores principales: Mizutani, Natsuki, Kawanabe, Akira, Jinno, Yuka, Narita, Hirotaka, Yonezawa, Tomoko, Nakagawa, Atsushi, Okamura, Yasushi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245683/
https://www.ncbi.nlm.nih.gov/pubmed/35733115
http://dx.doi.org/10.1073/pnas.2200364119
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author Mizutani, Natsuki
Kawanabe, Akira
Jinno, Yuka
Narita, Hirotaka
Yonezawa, Tomoko
Nakagawa, Atsushi
Okamura, Yasushi
author_facet Mizutani, Natsuki
Kawanabe, Akira
Jinno, Yuka
Narita, Hirotaka
Yonezawa, Tomoko
Nakagawa, Atsushi
Okamura, Yasushi
author_sort Mizutani, Natsuki
collection PubMed
description 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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spelling pubmed-92456832022-12-21 Interaction between S4 and the phosphatase domain mediates electrochemical coupling in voltage-sensing phosphatase (VSP) Mizutani, Natsuki Kawanabe, Akira Jinno, Yuka Narita, Hirotaka Yonezawa, Tomoko Nakagawa, Atsushi Okamura, Yasushi Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2022-06-21 2022-06-28 /pmc/articles/PMC9245683/ /pubmed/35733115 http://dx.doi.org/10.1073/pnas.2200364119 Text en Copyright © 2022 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Mizutani, Natsuki
Kawanabe, Akira
Jinno, Yuka
Narita, Hirotaka
Yonezawa, Tomoko
Nakagawa, Atsushi
Okamura, Yasushi
Interaction between S4 and the phosphatase domain mediates electrochemical coupling in voltage-sensing phosphatase (VSP)
title Interaction between S4 and the phosphatase domain mediates electrochemical coupling in voltage-sensing phosphatase (VSP)
title_full Interaction between S4 and the phosphatase domain mediates electrochemical coupling in voltage-sensing phosphatase (VSP)
title_fullStr Interaction between S4 and the phosphatase domain mediates electrochemical coupling in voltage-sensing phosphatase (VSP)
title_full_unstemmed Interaction between S4 and the phosphatase domain mediates electrochemical coupling in voltage-sensing phosphatase (VSP)
title_short Interaction between S4 and the phosphatase domain mediates electrochemical coupling in voltage-sensing phosphatase (VSP)
title_sort interaction between s4 and the phosphatase domain mediates electrochemical coupling in voltage-sensing phosphatase (vsp)
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9245683/
https://www.ncbi.nlm.nih.gov/pubmed/35733115
http://dx.doi.org/10.1073/pnas.2200364119
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