Interaction between S4 and the phosphatase domain mediates electrochemical coupling in voltage-sensing phosphatase (VSP)

被引：9
|
作者：
Mizutani, Natsuki [5 ]
Kawanabe, Akira [1 ,5 ]
Jinno, Yuka [2 ,5 ]
Narita, Hirotaka [3 ,6 ]
Yonezawa, Tomoko [4 ,5 ]
Nakagawa, Atsushi [6 ]
Okamura, Yasushi [5 ,7 ]
机构：
[1] Kagawa Univ, Fac Med, Lab Mol Physiol & Biophys, Miki Cho, Takamatsu, Kagawa 7610793, Japan
[2] Osaka Univ, Grad Sch Med, Dept Cardiovasc Med, Suita, Osaka 5650871, Japan
[3] Japan Aerosp Explorat Agcy, Tsukuba, Ibaraki 3058505, Japan
[4] Osaka Univ, Ctr Med Res & Educ, Grad Sch Med, Suita, Osaka 5650871, Japan
[5] Osaka Univ, Grad Sch Med, Dept Physiol, Lab Integrat Physiol, Suita, Osaka 5650871, Japan
[6] Osaka Univ, Inst Prot Res, Suita, Osaka 5650871, Japan
[7] Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2022年 / 119卷 / 26期
基金：
日本学术振兴会; 日本科学技术振兴机构;
关键词：
voltage-sensing phosphatase; voltage sensor domain; hydrophobicity; Anap; phosphoinositide; TUMOR-SUPPRESSOR; STRUCTURAL BASIS; CI-VSP; SUBSTRATE RECOGNITION; FLUORESCENT-PROBE; CRYSTAL-STRUCTURE; PTEN; SENSOR; PHOSPHORYLATION; ASSOCIATION;
D O I：
10.1073/pnas.2200364119
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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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页数：12
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