Electro-chemical coupling in the voltage-dependent phosphatase Ci-VSP
| Autor: | Lijun Liu, Daniel L. Minor, Ehud Y. Isacoff, Qiang Xu, Susy C. Kohout, Sarah C. Bell |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Phosphoric monoester hydrolases Voltage clamp Phosphatase medicine.disease_cause Electrochemistry Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Catalytic Domain medicine Animals Phosphatidylinositol Molecular Biology 030304 developmental biology 0303 health sciences Mutation Chemistry Cell Biology Phosphoric Monoester Hydrolases Coupling (electronics) Electrophysiology Biochemistry Biophysics 030217 neurology & neurosurgery |
| Zdroj: | Nature chemical biology |
| ISSN: | 1552-4469 1552-4450 |
| Popis: | In the voltage-sensing phosphatase Ci-VSP, a voltage-sensing domain (VSD) controls a lipid phosphatase domain (PD). The mechanism by which the domains are allosterically coupled is not well understood. Using an in vivo assay, we found that the interdomain linker that connects the VSD to the PD is essential for coupling the full-length protein. Biochemical assays showed that the linker is also needed for activity in the isolated PD. We also identified a late step of VSD motion in the full-length protein that depends on the linker. Notably, we found that this VSD motion requires PI(4,5)P2, a substrate of Ci-VSP. These results suggest that the voltage-driven motion of the VSD turns the enzyme on by rearranging the linker into an activated conformation, and that this activated conformation is stabilized by PI(4,5)P2. We propose that Ci-VSP activity is self-limited because its decrease of PI(4,5)P2 levels decouples the VSD from the enzyme. |
| Databáze: | OpenAIRE |
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