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Detection of Protein S-Acylation using Acyl-Resin Assisted Capture
Published on: April 10, 2020
The GCP16-zDHHC9 S-acyltransferase complex: Reciprocal effects on protein S-acylation and stability
Despoina Allagioti1, Andrew J Thompson2, Mohammad A Al-Mhadeen3
1Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
The Journal of Biological Chemistry
|July 21, 2026
Summary
GCP16 protein enhances the stability and S-acylation of the zDHHC9 enzyme, while zDHHC9 reciprocally boosts GCP16
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- S-acylation, a critical post-translational modification, is catalyzed by zinc-dependent zDHHC enzymes.
- The zDHHC9 enzyme forms a complex with GCP16, an accessory protein, influencing its activity.
- The precise bidirectional regulatory effects of the zDHHC9-GCP16 interaction in mammalian cells remain incompletely understood.
Purpose of the Study:
- To elucidate the bidirectional regulatory effects of the zDHHC9-GCP16 interaction on protein S-acylation and stability.
- To investigate the role of S-acylation in the stability of GCP16 and its interaction with zDHHC9.
- To determine the functional significance of the zDHHC9-GCP16 complex in cellular processes.
Main Methods:
- Investigated the effects of GCP16 on zDHHC9 S-acylation and stability using biochemical assays.
- Analyzed the reciprocal effects of zDHHC9 on GCP16 S-acylation and stability.
- Utilized site-directed mutagenesis to probe the importance of zDHHC9-GCP16 binding interfaces.
- Assessed the functional impact of the zDHHC9-GCP16 complex on dendritic growth in hippocampal neurons.
Main Results:
- GCP16 enhances both the S-acylation and stability of zDHHC9, without affecting zDHHC3.
- zDHHC9 reciprocally enhances the S-acylation and stability of GCP16.
- S-acylation of GCP16, particularly in its hydrophobic helical regions, appears to protect it from proteasomal degradation.
- Mutations disrupting the zDHHC9-GCP16 interface abolish the bidirectional regulatory effects and impair dendritic growth.
Conclusions:
- The zDHHC9-GCP16 interaction is bidirectional, with mutual enhancement of S-acylation and stability.
- S-acylation plays a crucial role in stabilizing GCP16 by preventing its degradation.
- The formation of a stable zDHHC9-GCP16 complex is essential for its function, including supporting neuronal development.
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