Central Role of the Lowest Part of S4 of CI-VSP in Coupling Mechanism

Abstract

Voltage-sensing phosphatase (VSP) consists of voltage sensor domain (VSD) and the cytoplasmic catalytic region (CCR), exhibiting phosphatase activity mainly toward phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) upon membrane depolarization. It has been reported that activation of VSD tightly couples with phosphatase activity, however, it is still unclear how VSD induces phosphatase activity. Since the lower part of S4 is close to the CCR, we predict that this part plays important roles in inducing phosphatase activity.