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Updated: Nov 14, 2025
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Acyl-PEGyl Exchange Gel Shift Assay for Quantitative Determination of Palmitoylation of Brain Membrane Proteins
Published on: March 29, 2020
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Palmitoylated acyl protein thioesterase APT2 deforms membranes to extract substrate acyl chains
Laurence Abrami1, Martina Audagnotto2, Sylvia Ho1
1Global Health Institute, School of Life Sciences, EPFL, Lausanne, Switzerland.
Nature Chemical Biology
|March 12, 2021
Summary
Acyl protein thioesterase 2 (APT2) binds membranes via electrostatic attraction, hydrophobic insertion, and palmitoylation. Membrane binding protects APT2 from degradation, enabling protein deacylation.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Protein S-acylation is a key posttranslational modification regulating protein function.
- Acyl protein thioesterases (APTs) reverse S-acylation but their mechanisms are poorly understood.
- APT2 (LYPLA2) is a major cellular thioesterase involved in deacylation.
Purpose of the Study:
- To elucidate the molecular mechanism of APT2 (LYPLA2) action.
- To understand how APT2 interacts with cellular membranes.
- To investigate the regulation of APT2 activity and stability.
Main Methods:
- Computational modeling
- In vitro biochemical assays
- Proteasomal degradation assays
- Membrane binding studies
Main Results:
- Soluble APT2 is prone to proteasomal degradation.
- Membrane binding, involving electrostatic attraction, hydrophobic loop insertion, and palmitoylation by ZDHHC3/7, stabilizes APT2.
- APT2 is predicted to deform lipid bilayers to access and hydrolyze acyl chains from substrates.
Conclusions:
- Membrane association is critical for APT2 stability and function.
- The study provides a molecular framework for APT2-mediated deacylation.
- Understanding APT2 dynamics is crucial for comprehending protein regulation in the endomembrane system.
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