9C49

Cryo-EM structure of Danio rerio voltage-sensing phosphatase (VSP) phosphatase domain

Summary for 9C49

• Entry DOI: 10.2210/pdb9c49/pdb
• EMDB information: 45178
• Descriptor: Phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase TPTE2 (1 entity in total)
• Functional Keywords: phosphatase, voltage-sensing, membrane protein
• Biological source: Danio rerio (zebrafish)
• Total number of polymer chains: 2
• Total formula weight: 119281.04

Authors

Zhang, L.,Brohawn, S.G. (deposition date: 2024-06-03, release date: 2024-07-10, Last modification date: 2024-08-14)

Primary citation

Yu, Y.,Zhang, L.,Li, B.,Fu, Z.,Brohawn, S.G.,Isacoff, E.Y.
Coupling sensor to enzyme in the voltage sensing phosphatase.
Nat Commun, 15:6409-6409, 2024

PubMed 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.

PubMed: 39080263
DOI: 10.1038/s41467-024-50319-8

Experimental method

ELECTRON MICROSCOPY (2.97 Å)