Domain-to-domain coupling in voltage-sensing phosphatase

• Published in: Biophysics and Physicobiology 2017, Vol.14, pp.85-97
• Main Authors: Sakata, Souhei, Matsuda, Makoto, Kawanabe, Akira, Okamura, Yasushi
• Format: Article
• Language: English
• Subjects: ion channel; membrane potential; phosphoinositide; Review
• ISSN: 2189-4779; 2189-4779
• DOI: 10.2142/biophysico.14.0_85

Voltage-sensing phosphatase (VSP) consists of a transmembrane voltage sensor and a cytoplasmic enzyme region. The enzyme region contains the phosphatase and C2 domains, is structurally similar to the tumor suppressor phosphatase PTEN, and catalyzes the dephosphorylation of phosphoinositides. The transmembrane voltage sensor is connected to the phosphatase through a short linker region, and phosphatase activity is induced upon membrane depolarization. Although the detailed molecular characteristics of the voltage sensor domain and the enzyme region have been revealed, little is known how these two regions are coupled. In addition, it is important to know whether mechanism for coupling between the voltage sensor domain and downstream effector function is shared among other voltage sensor domain-containing proteins. Recent studies in which specific amino acid sites were genetically labeled using a fluorescent unnatural amino acid have enabled detection of the local structural changes in the cytoplasmic region of Ciona intestinalis VSP that occur with a change in membrane potential. The results of those studies provide novel insight into how the enzyme activity of the cytoplasmic region of VSP is regulated by the voltage sensor domain.