Electrochemical coupling in the voltage-dependent phosphatase Ci-VSP

Nat Chem Biol. 2010 May;6(5):369-75. doi: 10.1038/nchembio.349. Epub 2010 Apr 4.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Catalytic Domain
  • Electrochemistry / methods*
  • Mutation
  • Phosphoric Monoester Hydrolases / chemistry*
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / metabolism

Substances

  • voltage-sensor-containing phosphatase, Ciona intestinalis
  • Phosphoric Monoester Hydrolases

Associated data

  • PubChem-Substance/89650243
  • PubChem-Substance/89650244
  • PubChem-Substance/89650245