Coupling sensor to enzyme in the voltage sensing phosphatase.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39080263.
- Also identified by DOI 10.1038/s41467-024-50319-8 and PMC identifier 11289409.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Voltage-sensing phosphatases (VSPs) dephosphorylate phosphoinositide (PIP) signaling lipids in response to membrane depolarization. VSPs possess an S4-containing voltage sensor domain (VSD), resembling that of voltage-gated cation channels, and a lipid phosphatase domain (PD). The mechanism by which voltage turns on enzyme activity is unclear. Structural analysis and modeling suggest several sites of VSD-PD interaction that could couple voltage sensing to catalysis. Voltage clamp fluorometry reveals voltage-driven rearrangements in three sites implicated earlier in enzyme activation-the VSD-PD linker, gating loop and R loop-as well as the N-terminal domain, which has not yet been explored. N-terminus mutations perturb both rearrangements in the other segments and enzyme activity. Our results provide a model for a dynamic assembly by which S4 controls the catalytic site.
Medical subject headings
- Phosphoric Monoester Hydrolases
- Catalytic Domain