P-selectin is acylated with palmitic acid and stearic acid at cysteine 766 through a thioester linkage

Fujimoto, Tsutomu; Stroud, Eric D.; Whatley, Ralph E.; Prescott, Stephen M.; Muszbek, László; Laposata, Michael; McEver, Rodger P.

doi:10.1016/s0021-9258(18)82137-8

Cited by 59 publications

(10 citation statements)

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“…Although this attachment is the most likely event, a general lack of mass spectrometry (MS) data confirming the identity of the modification catalyzed by individual DHHCs leaves open the possibility that other acyl groups are being attached by this family of PATs. This possibility is supported by the observation that other fatty acids, such as arachidonate, eicosapentaenoate, palmitoleic acid, and stearic acid, reportedly attach to protein substrates through thioester bonds. − Cysteines modified with 14:0, 18:0, 18:1, and 18:2 fatty acids were detected in bovine heart and liver tissue . S-Acylation with stearate and arachidonate also occurs on the Gα subunit, myelin, the G2 protein of the Rift Valley fever virus, and the asialoglycoprotein receptor. ,,− …”

Section: Cysteine Palmitoylationmentioning

confidence: 89%

Protein Lipidation: Occurrence, Mechanisms, Biological Functions, and Enabling Technologies

et al. 2018

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Protein lipidation, including cysteine prenylation, N-terminal glycine myristoylation, cysteine palmitoylation, and serine and lysine fatty acylation, occurs in many proteins in eukaryotic cells and regulates numerous biological pathways, such as membrane trafficking, protein secretion, signal transduction, and apoptosis. We provide a comprehensive review of protein lipidation, including descriptions of proteins known to be modified and the functions of the modifications, the enzymes that control them, and the tools and technologies developed to study them. We also highlight key questions about protein lipidation that remain to be answered, the challenges associated with answering such questions, and possible solutions to overcome these challenges.

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Section: Cysteine Palmitoylationmentioning

confidence: 89%

Protein Lipidation: Occurrence, Mechanisms, Biological Functions, and Enabling Technologies

et al. 2018

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“…VARIETY of integral membrane proteins and reversibly membrane-associated proteins in eukaryotic cells exhibits posttranslational acylation on one or more cysteine residues, a modification that for a number of such proteins appears to be dynamic (6,39,42,45,81,82,84) and, in some cases, is modulated by physiological or pharmacological stimuli (15,31,45,46,63,86). Integral membrane proteins may be S-acylated either on cysteine residues near the cytoplasmic termini of transmembrane helixes (3,14,28,30,32,68,74) or on cytoplasmic cysteine residues more distant from a transmembrane helix (9,18,21,88). Among the reversibly membrane-associated proteins that undergo S-acylation are found a number of srchomologous nonreceptor tyrosine kinases, heterotrimeric G protein a subunits and monomeric G proteins (for reviews see 10,43,44,61,65,75).…”

mentioning

confidence: 99%

Lipid-modified, cysteinyl-containing peptides of diverse structures are efficiently S-acylated at the plasma membrane of mammalian cells.

Schroeder

Leventis

Shahinian

et al. 1996

The Journal of Cell Biology

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Abstract. A variety of cysteine-containing, lipidmodified peptides are found to be S-acylated by cultured mammalian cells. The acylation reaction is highly specific for cysteinyl over serinyl residues and for lipid-modified peptides over hydrophilic peptides. The S-acylation process appears by various criteria to be enzymatic and resembles the S-acylation of plasma membrane-associated proteins in various characteristics, including inhibition by tunicamycin. The substrate range of the S-acylation reaction encompasses, but is not limited to, lipopeptides incorporating the motifs myristoylGC-and -CXC(farnesyl)-OCH3, which are reversibly S-acylated in various intracellular proteins. Mass-spectrometric analysis indicates that palmitoyl residues constitute the predominant but not the only type of S-acyl group coupled to a lipopeptide carrying the myristoylGC-motif, with smaller amounts of S-stearoyl and S-oleoyl substituents also detectable. Fluorescence microscopy using NBD-labeled cysteinyl lipopeptides reveals that the products of lipopeptide S-acylation, which cannot diffuse between membranes, are in almost all cases localized preferentially to the plasma membrane. This preferential localization is found even at reduced temperatures where vesicular transport from the Golgi complex to the plasma membrane is suppressed, strongly suggesting that the plasma membrane itself is the preferred site of S-acylation of these species. Uniquely among the lipopeptides studied, species incorporating an unphysiological N-myristoylcysteinyl-motif also show substantial formation of S-acylated products in a second, intracellular compartment identified as the Golgi complex by its labeling with a fluorescent ceramide. Our results suggest that distinct S-acyltransferases exist in the Golgi complex and plasma membrane compartments and that S-acylation of motifs such as myristoylGC-occurs specifically at the plasma membrane, affording efficient targeting of cellular proteins bearing such motifs to this membrane compartment.VARIETY of integral membrane proteins and reversibly membrane-associated proteins in eukaryotic cells exhibits posttranslational acylation on one or more cysteine residues, a modification that for a number of such proteins appears to be dynamic (6,39,42,45,81,82,84) and, in some cases, is modulated by physiological or pharmacological stimuli (15,31,45,46,63,86). Integral membrane proteins may be S-acylated either on cysteine residues near the cytoplasmic termini of transmembrane helixes (3,14,28,30,32,68,74) or on cytoplasmic cysteine residues more distant from a transmembrane helix (9,18,21,88). Among the reversibly membrane-associated proteins that undergo S-acylation are found a number of srchomologous nonreceptor tyrosine kinases, heterotrimeric G protein a subunits and monomeric G proteins (for reviews see 10,43,44,61,65,75). S-acylation has been shown to enhance the membrane association of a variety Address all correspondence to Dr. John R. Silvius, Department of Biochemistry, McGill University, Montrral, Qu6bec,...

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“…The ability to incorporate different lengths of fatty acyl chains into protein substrates varies across the known zDHHCs. , In particular, zDHHC7 efficiently catalyzes stearoylation of SNAP25, indicating that zDHHCs facilitate lipid modifications beyond S- palmitoylation . Only a handful of human and viral S -stearoylated proteins are known. − The S-stearoylation on viral spike proteins is essential for host–membrane fusion but is not mechanistically well-understood . The functional role of protein stearoylation in humans is not clearly defined as well.…”

Section: Biological Applications In Other Lipidsmentioning

confidence: 99%

A Not-So-Ancient Grease History: Click Chemistry and Protein Lipid Modifications

2021

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Protein lipid modification involves the attachment of hydrophobic groups to proteins via ester, thioester, amide, or thioether linkages. In this review, the specific click chemical reactions that have been employed to study protein lipid modification and their use for specific labeling applications are first described. This is followed by an introduction to the different types of protein lipid modifications that occur in biology. Next, the roles of click chemistry in elucidating specific biological features including the identification of lipid-modified proteins, studies of their regulation, and their role in diseases are presented. A description of the use of protein–lipid modifying enzymes for specific labeling applications including protein immobilization, fluorescent labeling, nanostructure assembly, and the construction of protein–drug conjugates is presented next. Concluding remarks and future directions are presented in the final section.

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P-selectin is acylated with palmitic acid and stearic acid at cysteine 766 through a thioester linkage

Cited by 59 publications

References 1 publication

Protein Lipidation: Occurrence, Mechanisms, Biological Functions, and Enabling Technologies

Protein Lipidation: Occurrence, Mechanisms, Biological Functions, and Enabling Technologies

Lipid-modified, cysteinyl-containing peptides of diverse structures are efficiently S-acylated at the plasma membrane of mammalian cells.

A Not-So-Ancient Grease History: Click Chemistry and Protein Lipid Modifications

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