Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Feb 21;23(4):2365.
doi: 10.3390/ijms23042365.

Protein Lipidation Types: Current Strategies for Enrichment and Characterization

Rong Wang  1   2 , Yong Q Chen  1   2
Affiliations
Review

Protein Lipidation Types: Current Strategies for Enrichment and Characterization

Rong Wang et al. Int J Mol Sci. .

Abstract

Post-translational modifications regulate diverse activities of a colossal number of proteins. For example, various types of lipids can be covalently linked to proteins enzymatically or non-enzymatically. Protein lipidation is perhaps not as extensively studied as protein phosphorylation, ubiquitination, or glycosylation although it is no less significant than these modifications. Evidence suggests that proteins can be attached by at least seven types of lipids, including fatty acids, lipoic acids, isoprenoids, sterols, phospholipids, glycosylphosphatidylinositol anchors, and lipid-derived electrophiles. In this review, we summarize types of protein lipidation and methods used for their detection, with an emphasis on the conjugation of proteins with polyunsaturated fatty acids (PUFAs). We discuss possible reasons for the scarcity of reports on PUFA-modified proteins, limitations in current methodology, and potential approaches in detecting PUFA modifications.

Keywords: mass spectrometry; polyunsaturated fatty acid; protein lipidation; proteomics.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Various analytical methods to identify and characterize protein lipidations. (A) Radioactive isotope-labeling. Any type of protein lipidation can be identified using this method if the corresponding isotope-labeled lipid is available; (B) Antibody affinity enrichment. In general, any type of protein lipidation can be detected if a suitable pan-antibody is available; (C–E) ABE and similar methods. These methods are used for detecting S-pamitoylation; (F) Click chemistry. Protein lipidations that can react with specific alkynyl/azide-lipid probes can be identified; (G) Biotin hydrazide affinity capture. Only proteins containing carbonyl or aldehyde groups are suitable for this method to detect the LDE modifications; (H) Lipid esterification. Some saturated or unsaturated fatty acid moieties derived from protein acylations can be identified if the process of esterification on dissociative lipid (usually hydrolysis) is available.
Figure 2
Figure 2
Methods to detect PUFA-modified proteins. (A) Flowchart of ABE and GC/LC-MS. Group A treats the supernatant from the acetone precipitation in cells; Group B treats the precipitation from the acetone precipitation in cells; Group C1 and D1 (+NH2OH group) add NH2OH and acetone to the above precipitation and further treats the second supernatant and precipitation as group C1 and D1; Group C2 and D2 (-NH2OH group) add control and acetone to the above precipitation and further treats the second supernatant and precipitation as group C2 and D2; (B) The synthesis of the alkynyl-linoleic acid (alk-LA) probe. (C) Flowchart of the Click-chemistry method employed on total-protein or membrane-protein samples.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Mann M., Jensen O.N. Proteomic analysis of post-translational modifications. Nat. Biotechnol. 2003;21:255–261. doi: 10.1038/nbt0303-255. - DOI - PubMed
    1. Keenan E.K., Zachman D.K., Hirschey M.D. Discovering the landscape of protein modifications. Mol. Cell. 2021;81:1868–1878. doi: 10.1016/j.molcel.2021.03.015. - DOI - PMC - PubMed
    1. Zavialova M.G., Zgoda V.G., Nikolaev E.N. Analysis of contribution of protein phosphorylation in the development of the diseases. Biomeditsinskaia Khimiia. 2017;63:101–114. doi: 10.18097/PBMC20176302101. - DOI - PubMed
    1. Cifani P., Kentsis A. Towards comprehensive and quantitative proteomics for diagnosis and therapy of human disease. Proteomics. 2017;17:1600079. doi: 10.1002/pmic.201600079. - DOI - PMC - PubMed
    1. Yang M., Zhang Y., Ren J. Acetylation in cardiovascular diseases: Molecular mechanisms and clinical implications. Biochim. et Biophys. Acta (BBA)—Mol. Basis Dis. 2020;1866:165836. doi: 10.1016/j.bbadis.2020.165836. - DOI - PubMed

LinkOut - more resources