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Updated: Jan 18, 2026
Acyl-PEGyl Exchange Gel Shift Assay for Quantitative Determination of Palmitoylation of Brain Membrane Proteins
Published on: March 29, 2020
Functional dissection of the zDHHC palmitoyltransferase 5-golgin A7 palmitoylation complex
Martha A Kahlson1, Joan Ritho1, João Victor Gomes2
1Department of Biology, Stanford University, Stanford, California, USA.
Abstract:
Small molecules serve as valuable tools for probing nonapoptotic cell death mechanisms. The small molecule caspase independent lethal 56 (CIL56) induces a unique form of nonapoptotic cancer cell death that is promoted by a complex formed between zDHHC palmitoyltransferase 5 (ZDHHC5) and an accessory protein, golgin A7 (GOLGA7, also known as GCP16). The structure and function of this complex in nonapoptotic cell death regulation remain poorly understood. Here, we use coimmunoprecipitation, functional assays, and cryogenic electron microscopy (cryo-EM) to elucidate the structure and function of the Zdhhc5-GOLGA7 complex. We identify key residues in both Zdhhc5 and GOLGA7 that are necessary for complex formation and to promote nonapoptotic cancer cell death in response to caspase independent lethal 56. These results provide new insights into the structure and function of a death-promoting protein complex.
Insights
The small molecule caspase independent lethal 56 (CIL56) triggers nonapoptotic cancer cell death. Researchers elucidated the structure of the ZDHHC5-GOLGA7 complex, identifying key residues essential for CIL56-induced cell death.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Small molecules are crucial for studying nonapoptotic cell death pathways.
- The caspase independent lethal 56 (CIL56) molecule induces a specific form of nonapoptotic cancer cell death.
- This cell death is facilitated by a complex involving zDHHC palmitoyltransferase 5 (ZDHHC5) and golgin A7 (GOLGA7).
Purpose of the Study:
- To investigate the structure and function of the ZDHHC5-GOLGA7 complex.
- To understand the complex's role in regulating nonapoptotic cell death.
- To identify molecular determinants of ZDHHC5-GOLGA7 complex formation and function.
Main Methods:
- Coimmunoprecipitation assays to study protein interactions.
- Functional assays to assess cell death.
- Cryogenic electron microscopy (cryo-EM) for structural determination.
Main Results:
- The study elucidated the structure of the ZDHHC5-GOLGA7 complex.
- Key amino acid residues in both ZDHHC5 and GOLGA7 were identified as critical for complex formation.
- These residues are necessary for promoting nonapoptotic cancer cell death induced by CIL56.
Conclusions:
- The ZDHHC5-GOLGA7 complex plays a significant role in promoting nonapoptotic cancer cell death.
- Structural insights into the complex provide a foundation for understanding its function.
- This research offers new perspectives on death-promoting protein complexes and potential therapeutic targets.
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