Protein fatty-acylation in eukaryotes has been associated with many fundamental biological processes. However, the diversity, abundance and regulatory mechanisms of protein fatty-acylation in vivo remain to be explored. Herein, we review the proteomic analysis of fatty-acylated proteins, with a focus on N-myristoylation and S-palmitoylation. We then highlight major challenges and emerging methods for direct site identification, quantitation, and lipid structure characterization to understand the functions and regulatory mechanisms of fatty-acylated proteins in physiology and disease.
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http://dx.doi.org/10.1016/j.cbpa.2015.11.008 | DOI Listing |
J Assist Reprod Genet
January 2025
Department of Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Pregnancy complications pose challenges for both pregnant women and obstetricians globally, with the pathogenesis of many remaining poorly understood. Recently coined as a mode of cell death, cuproptosis has been proposed but remains largely unexplored. This process involves copper overload, resulting in the accumulation of fatty acylated proteins and subsequent loss of iron-sulfur cluster proteins.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2024
Boyce Thompson Institute, Cornell University, Ithaca, NY 14853.
Protein lipidation plays critical roles in regulating protein function and localization. However, the chemical diversity and specificity of fatty acyl group utilization have not been investigated using untargeted approaches, and it is unclear to what extent structures and biosynthetic origins of -acyl moieties differ from - and -fatty acylation. Here, we show that fatty acylation patterns in differ markedly between different amino acid residues.
View Article and Find Full Text PDFBiochemistry
December 2023
Department of Molecular Biology, Rowan University School of Osteopathic Medicine, Stratford, New Jersey 08084, United States.
Human sirtuin isoform 2 (SIRT2) is an NAD-dependent enzyme that functions as a lysine deacetylase and defatty-acylase. Here, we report that SIRT2 readily dimerizes in solution and in cells and that dimerization affects its ability to remove different acyl modifications from substrates. Dimerization of recombinant SIRT2 was revealed with analytical size exclusion chromatography and chemical cross-linking.
View Article and Find Full Text PDFBioorg Med Chem Lett
June 2023
Graduate School of Agricultural and Life Sciences, The University of Tokyo, Yayoi 1-1-1, Bunkyo, Tokyo 113-8657, Japan; Collaborative Research Institute for Innovative Microbiology (CRIIM), The University of Tokyo, Yayoi 1-1-1, Bunkyo, Tokyo 113-8657, Japan. Electronic address:
Ribosomally synthesized and posttranslationally modified peptides (RiPPs) with polar-functionalized fatty acyl groups are newly found lipopeptide-class natural products. We recently employed a combined approach of genome mining and stable isotope labeling and discovered solabiomycins as one of the polar-functionalized fatty-acylated RiPPs (PFARs) from Streptomyces lydicus NBRC13058. The solabiomycins contained a characteristic sulfoxide group in the labionin moiety referred to as the 'solabionin' structure for the RiPP moiety.
View Article and Find Full Text PDFInt J Mol Sci
April 2023
Department of Enzymology, Charles Tanford Protein Center, Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, 06120 Halle, Germany.
Lysine deacetylases, like histone deacetylases (HDACs) and sirtuins (SIRTs), are involved in many regulatory processes such as control of metabolic pathways, DNA repair, and stress responses. Besides robust deacetylase activity, sirtuin isoforms SIRT2 and SIRT3 also show demyristoylase activity. Interestingly, most of the inhibitors described so far for SIRT2 are not active if myristoylated substrates are used.
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