S-acylation is a reversible lipid modification occurring on cysteine residues mediated by a family of membrane-bound 'zDHHC' enzymes. S-acylation predominantly results in anchoring of soluble proteins to membrane compartments or in the trafficking of membrane proteins to different compartments. Recent work has shown that although S-acylation of some proteins may involve very weak interactions with zDHHC enzymes, a pool of zDHHC enzymes exhibit strong and specific interactions with substrates, thereby recruiting them for S-acylation. For example, the ankyrin-repeat domains of zDHHC17 and zDHHC13 interact specifically with unstructured consensus sequences present in some proteins, thus contributing to substrate specificity of these enzymes. In addition to this new information on zDHHC enzyme protein substrate specificity, recent work has also identified marked differences in selectivity of zDHHC enzymes for acyl-CoA substrates and has started to unravel the underlying molecular basis for this lipid selectivity. This review will focus on the protein and acyl-CoA selectivity of zDHHC enzymes.
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Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome 00168, Italy.
Protein post-translational modifications (PTM) play a crucial role in the modulation of synaptic function and their alterations are involved in the onset and progression of neurodegenerative disorders. S-palmitoylation is a PTM catalyzed by zinc finger DHHC domain containing (zDHHC) S-acyltransferases that affects both localization and activity of proteins regulating synaptic plasticity and amyloid-β (Aβ) metabolism. Here, we found significant increases of both zDHHC7 expression and protein S-palmitoylation in hippocampi of both 3×Tg-AD mice and post-mortem Alzheimer's disease (AD) patients.
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November 2024
Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan 421001, China. Electronic address:
Article Synopsis
- The ZDHHC13/ZDHHC17 subfamily is part of the ZDHHC family and is linked to important biological processes like S-palmitoylation and Mg transport.
- This subfamily is implicated in the development of several diseases, including Huntington's disease, osteoporosis, and cancer.
- The review covers the distribution, structure, and biological functions of ZDHHC13/ZDHHC17, emphasizing the need for more research to understand their role in disease mechanisms.
Exploring Protein -Palmitoylation: Mechanisms, Detection, and Strategies for Inhibitor Discovery.
ACS Chem Biol
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Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 116023, Dalian, China.
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Center for Metabolism Research, The Fourth Affiliated Hospital of School of Medicine and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China.
Lipid droplets (LDs) are organelles specialized in the storage of neutral lipids, cholesterol esters and triglycerides, thereby protecting cells from the toxicity of excess lipids while allowing for the mobilization of lipids in times of nutrient deprivation. Defects in LD function are associated with many diseases. S-acylation mediated by zDHHC acyltransferases modifies thousands of proteins, yet the physiological impact of this post-translational modification on individual proteins is poorly understood.
View Article and Find Full Text PDFMAVS Cys508 palmitoylation promotes its aggregation on the mitochondrial outer membrane and antiviral innate immunity.
Proc Natl Acad Sci U S A
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Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853.
Cysteine palmitoylation or -palmitoylation catalyzed by the ZDHHC family of acyltransferases regulates the biological function of numerous mammalian proteins as well as viral proteins. However, understanding of the role of -palmitoylation in antiviral immunity against RNA viruses remains very limited. The adaptor protein MAVS forms functionally essential prion-like aggregates upon activation by viral RNA-sensing RIG-I-like receptors.
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