Molecular mechanism of the substrate selectivity in Voltage-sensing phosphatase

2015 Fiscal Year Final Research Report

• Project/Area Number: 25860163
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General physiology
• Research Institution: Osaka Medical College (2015); Osaka University (2013-2014)
• Principal Investigator: SAKATA Souhei 大阪医科大学, 医学部, 講師 (40528006)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 膜電位 / イノシトールリン脂質 / 非天然アミノ酸 / 電位依存性ホスファターゼ

Outline of Final Research Achievements

Voltage-sensing phosphatase, VSP, has an activity to dephosphorylate several kinds of phosphoinositides in a voltage-dependent manner. Our recent study has shown that VSP mainly dephosphoryltaes PI(3,4,5)P3 in low membrane voltages but dephosphorylates PI(3,4)P2 in high voltages. However, little is know about the molecular mechanisms how the membrane voltage regulates the substrate specificity of VSP. In this work, I introduced a fluorescent label using the method of the genetic incorporation of a fluorescent unnatural amino acid to reveal the conformational change of the catalytic region which is responsible for the dephosphorylation activity. Results showed that Cα2 loop located in the catalytic region plays key roles in the substrate specificity in VSP.

Free Research Field

生理学