Home LiteratureArticle Details
PMID: 3517877 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Protein fatty acid acylation: enzymatic synthesis of an N-myristoylglycyl peptide.

Towler D, Glaser L

Abstract

Incubation of Saccharomyces cerevisiae strain JR153 with either [3H]myristate or [3H]palmitate demonstrates the synthesis of proteins that contain covalently bound fatty acids. A unique set of proteins is labeled by each fatty acid. Detailed analysis of a 20-kDa protein labeled with myristic acid demonstrates that myristate is linked to the amino-terminal glycine. We describe an enzymatic activity in yeast that will transfer myristic acid to the amino terminus of the octapeptide Gly-Asn-Ala-Ala-Ala-Ala-Arg-Arg, whose sequence was derived from a known N-myristoylated acyl protein, the catalytic subunit of cAMP-dependent protein kinase of bovine cardiac muscle. The acylation reaction is dependent on ATP and CoA, is enriched in a crude membrane fraction, and will use myristate but not palmitate as the acyl donor. Specificity of the glycyl peptide substrate is demonstrated by the observation that other glycyl peptides do not competitively inhibit myristoylation of Gly-Asn-Ala-Ala-Ala-Ala-Arg-Arg.

MeSH Terms
Acylation Adenosine Triphosphate/pharmacology Amino Acid Sequence Coenzyme A Ligases/pharmacology Glycine/metabolism Myristic Acid Myristic Acids/metabolism Palmitic Acid Palmitic Acids/metabolism Peptides/metabolism Saccharomyces cerevisiae/metabolism Tritium
Chemicals
Myristic Acids Palmitic Acids Peptides Myristic Acid Tritium Palmitic Acid Adenosine Triphosphate Coenzyme A Ligases Glycine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Towler D
Glaser L
References (37)
37 references, click to expand
  1. The antibiotic cerulenin, a novel tool for biochemistry as an inhibitor of fatty acid synthesis.
    Bacteriol Rev. 1976 Sep;40(3):681-97 PMID: 791237
  2. Acylation of cellular proteins with endogenously synthesized fatty acids.
    Biochemistry. 1986 Feb 25;25(4):878-84 PMID: 3964651
  3. Fatty acid binding to vesicular stomatitis virus glycoprotein: a new type of post-translational modification of the viral glycoprotein.
    Cell. 1979 Aug;17(4):813-9 PMID: 226266
  4. Primary structural requirements for N-glycosylation of peptides in rat liver.
    FEBS Lett. 1979 Dec 15;108(2):341-4 PMID: 520572
  5. Covalent binding of fatty acid to the transferrin receptor in cultured human cells.
    J Biol Chem. 1981 May 25;256(10):4715-8 PMID: 6262300
  6. Mutant defective in processing of an enzyme located in the lysosome-like vacuole of Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 1981 Jan;78(1):435-9 PMID: 7017716
  7. Early and late functions associated with the Golgi apparatus reside in distinct compartments.
    Proc Natl Acad Sci U S A. 1981 Dec;78(12):7453-7 PMID: 6801652
  8. In vivo acylation of rat brain myelin proteolipid protein.
    J Biol Chem. 1982 Apr 25;257(8):4588-92 PMID: 7068653
  9. Phosphorylation of synthetic peptides by a tyrosine protein kinase from the particulate fraction of a lymphoma cell line.
    Proc Natl Acad Sci U S A. 1982 Jan;79(2):282-6 PMID: 6804939
  10. Cerulenin blocks fatty acid acylation of glycoproteins and inhibits vesicular stomatitis and Sindbis virus particle formation.
    J Biol Chem. 1982 Sep 10;257(17):9887-90 PMID: 6286658
  11. n-Tetradecanoyl is the NH2-terminal blocking group of the catalytic subunit of cyclic AMP-dependent protein kinase from bovine cardiac muscle.
    Proc Natl Acad Sci U S A. 1982 Oct;79(20):6128-31 PMID: 6959104
  12. The transforming proteins of Rous sarcoma virus, Harvey sarcoma virus and Abelson virus contain tightly bound lipid.
    Cell. 1982 Dec;31(2 Pt 1):465-74 PMID: 6297767
  13. Identification of the NH2-terminal blocking group of calcineurin B as myristic acid.
    FEBS Lett. 1982 Dec 27;150(2):314-8 PMID: 7160476
  14. Dissection of the Golgi complex. II. Density separation of specific Golgi functions in virally infected cells treated with monensin.
    J Cell Biol. 1983 Mar;96(3):851-6 PMID: 6403555
  15. Myristyl amino-terminal acylation of murine retrovirus proteins: an unusual post-translational proteins modification.
    Proc Natl Acad Sci U S A. 1983 Jan;80(2):339-43 PMID: 6340098
  16. Substrate recognition by oligosaccharyltransferase. Studies on glycosylation of modified Asn-X-Thr/Ser tripeptides.
    J Biol Chem. 1983 Oct 10;258(19):11856-63 PMID: 6413505
  17. Substrate recognition by oligosaccharyl transferase. Inhibition of co-translational glycosylation by acceptor peptides.
    J Biol Chem. 1983 Dec 25;258(24):15255-60 PMID: 6686231
  18. Release of fatty acids from virus glycoproteins by hydroxylamine.
    Biochim Biophys Acta. 1984 Apr 10;798(2):156-66 PMID: 6324873
  19. Alpha and beta subunits of the nicotinic acetylcholine receptor contain covalently bound lipid.
    J Biol Chem. 1984 May 10;259(9):5364-7 PMID: 6715346
  20. Fatty acid-acylated proteins in secretory mutants of Saccharomyces cerevisiae.
    Mol Cell Biol. 1984 Apr;4(4):688-94 PMID: 6371494
  21. Cysteines in the transmembrane region of major histocompatibility complex antigens are fatty acylated via thioester bonds.
    J Biol Chem. 1984 Jun 10;259(11):7230-8 PMID: 6373770
  22. Cell-free fatty acid acylation of Semliki Forest viral polypeptides with microsomal membranes from eukaryotic cells.
    J Biol Chem. 1984 Jun 10;259(11):7245-52 PMID: 6725287
  23. Characterization of mucus glycoprotein fatty acyltransferase from gastric mucosa.
    J Biol Chem. 1984 Nov 10;259(21):13304-8 PMID: 6490656
  24. Identification of the NH2-terminal blocking group of NADH-cytochrome b5 reductase as myristic acid and the complete amino acid sequence of the membrane-binding domain.
    J Biol Chem. 1984 Nov 10;259(21):13349-54 PMID: 6436247
  25. A short sequence in the p60src N terminus is required for p60src myristylation and membrane association and for cell transformation.
    Mol Cell Biol. 1984 Sep;4(9):1834-42 PMID: 6092942
  26. In vitro acylation of the transferrin receptor.
    J Biol Chem. 1984 Dec 25;259(24):15460-3 PMID: 6096372
  27. Covalently bound myristate in a lymphoma tyrosine protein kinase.
    Proc Natl Acad Sci U S A. 1984 Dec;81(24):7679-82 PMID: 6595656
  28. Amino terminal myristylation of the protein kinase p60src, a retroviral transforming protein.
    Science. 1985 Jan 25;227(4685):427-9 PMID: 3917576
  29. Specificity of fatty acid acylation of cellular proteins.
    J Biol Chem. 1985 Mar 25;260(6):3784-90 PMID: 3972848
  30. Myristic acid is attached to the transforming protein of Rous sarcoma virus during or immediately after synthesis and is present in both soluble and membrane-bound forms of the protein.
    Mol Cell Biol. 1984 Dec;4(12):2697-704 PMID: 6441887
  31. An N-terminal peptide from p60src can direct myristylation and plasma membrane localization when fused to heterologous proteins.
    Nature. 1985 Mar 28-Apr 3;314(6009):374-7 PMID: 3920530
  32. Fine structural mapping of a critical NH2-terminal region of p60src.
    Proc Natl Acad Sci U S A. 1985 Mar;82(6):1623-7 PMID: 2984663
  33. Biosynthesis and modification of Golgi mannosidase II in HeLa and 3T3 cells.
    J Biol Chem. 1985 Jun 10;260(11):6654-62 PMID: 3922977
  34. Two classes of fatty acid acylated proteins exist in eukaryotic cells.
    EMBO J. 1985 May;4(5):1137-44 PMID: 2988939
  35. Studies on the attachment of myristic and palmitic acid to cell proteins in human squamous carcinoma cell lines: evidence for two pathways.
    EMBO J. 1985 May;4(5):1145-52 PMID: 4006909
  36. Mutation of NH2-terminal glycine of p60src prevents both myristoylation and morphological transformation.
    Proc Natl Acad Sci U S A. 1985 Jul;82(14):4625-8 PMID: 2991884
  37. A simplification of the protein assay method of Lowry et al. which is more generally applicable.
    Anal Biochem. 1977 Dec;83(2):346-56 PMID: 603028
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1986-05-00
Pages
2812-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC323396
Subset
IM
Grants
NIGMS NIH HHS · GM 18405 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]