Acylation of disc membrane rhodopsin may be nonenzymatic.

O’Brien, Paul; Jules, Robert St.; Reddy, T. Sanjeeva; Bazán, Nicolás G.; Zatz, Martin

doi:10.1016/s0021-9258(18)61175-5

Cited by 160 publications

(30 citation statements)

References 32 publications

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“…For instance, the transferrin receptor Trowbridge, 1987, 1990) and the cell surface glycoprotein CD4 (Crise and Rose, 1992) contain palmitoylated cysteines in their transmembrane domains. CD4 has a second palmitoylation site located one amino acid from the transmembrane domain whereas this distance is two amino acids in the HLA-D-associated invariant chain (Koch and Hiimmerling, 1986), six amino acids in vesicular stomatitis virus G protein (Rose et al, 1984), some subtypes of influenza virus hemagglutinin (Veit et al, 1991), and p63 (Schweizer et al, 1995), between 11 and 13 amino acids in f32-adrenergic receptor (O'Dowd et al, 1989), bovine opsin (Karnik et al, 1993), and bovine rhodopsin (O'Brien et al, 1987;Ovchinnikov et al, 1988;Papac et al, 1992) and 15-16 amino acids in the luteinizing hormone/human choriogonadotropin receptor (Kawate and Menon, 1994). The finding of palmitoylated cysteines located 29 and 33 amino acids from the transmembrane domain of the CD-MPR expands the possibilities for this covalent modification, and has interesting implications for the structure of the cytoplasmic tail of this receptor.…”

Section: Discussionmentioning

confidence: 99%

Cysteine34 of the cytoplasmic tail of the cation-dependent mannose 6-phosphate receptor is reversibly palmitoylated and required for normal trafficking and lysosomal enzyme sorting.

Schweizer

Kornfeld

Rohrer

1996

The Journal of Cell Biology

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Abstract. We have examined whether the two cysteine residues (Cys 3° and Cys 34) in the cytoplasmic tail of the cation-dependent mannose 6-phosphate receptor are palmitoylated via thioesters and whether these residues influence the biologic function of the receptor, To do this, mouse L cells expressing wild-type and mutant receptors were analyzed by metabolic labeling with [3H]palmitate, immunoprecipitation, and SDS-PAGE. Both Cys 3° and Cys 34 were found to be sites of palmitoylation and together they accounted for the total palmitoylation of the receptor. The palmitate rapidly turned over with a half-life of ~2 h compared to a halflife of greater than 40 h for the protein. These data suggest that palmitoylation of Cys 3° and Cys 34 leads to anchoring of this region of the cytoplasmic tail to the lipid bilayer. Anchoring via C y s 34 is essential for the normal trafficking and lysosomal enzyme sorting function of the receptor.

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Section: Discussionmentioning

confidence: 99%

Cysteine34 of the cytoplasmic tail of the cation-dependent mannose 6-phosphate receptor is reversibly palmitoylated and required for normal trafficking and lysosomal enzyme sorting.

Schweizer

Kornfeld

Rohrer

1996

The Journal of Cell Biology

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“…Apparently enzymic activities mediating S-acylation of protein substrates have been identified in several intact or solubilized membrane preparations (1,4,19,24,70,72) but to date have not been characterized at a molecular level. Certain integral membrane proteins (7,48,66) and even simple (lipo)peptides (5,27,57) have been shown to exhibit spontaneous S-acylation in vitro in the presence of long chain acyl-CoAs, although it remains to be determined whether such autocatalytic reactions can mediate the S-acylation of proteins in intact cells.…”

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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“…Though they are not representative of the entire S-acylated cellular proteome, one study conducted on platelet proteins found that, while the majority of thioester-linked fatty acids consisted of palmitate (about 74%), other fatty acids, such as stearate (C18:0) and oleate (C18:1) were also present [ 44 ]. Additionally, other studies have demonstrated that the diversity of acyl chain lengths observed on S-acylated proteins includes myristic acid (C14:0), palmitoleic acid (C16:1), linoleic acid (C18:2), arachidonic acid (C20:4) and eicosapentaenoic acid (C20:5) [ 45 ]; L [ 46 ]; P. [ 47 ]. As one might expect with such a diverse array of fatty acid substrates, it has been clearly demonstrated that different members of the zDHHC family have varying propensities for the assortment of acyl-CoA at their disposal [ 10 , 42 , 48 ].…”

Section: In Vitro Reconstitution and Acyl-coa Selectivitymentioning

confidence: 99%

In vitro reconstitution of substrate S-acylation by the zDHHC family of protein acyltransferases

Banerjee

2022

Open Biol.

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Protein S-acylation, more commonly known as protein palmitoylation, is a biological process defined by the covalent attachment of long chain fatty acids onto cysteine residues of a protein, effectively altering the local hydrophobicity and influencing its stability, localization and overall function. Observed ubiquitously in all eukaryotes, this post translational modification is mediated by the 23-member family of zDHHC protein acyltransferases in mammals. There are thousands of proteins that are S-acylated and multiple zDHHC enzymes can potentially act on a single substrate. Since its discovery, numerous methods have been developed for the identification of zDHHC substrates and the individual members of the family that catalyse their acylation. Despite these recent advances in assay development, there is a persistent gap in knowledge relating to zDHHC substrate specificity and recognition, that can only be thoroughly addressed through in vitro reconstitution. Herein, we will review the various methods currently available for reconstitution of protein S-acylation for the purposes of identifying enzyme–substrate pairs with a particular emphasis on the advantages and disadvantages of each approach.

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Acylation of disc membrane rhodopsin may be nonenzymatic.

Cited by 160 publications

References 32 publications

Cysteine34 of the cytoplasmic tail of the cation-dependent mannose 6-phosphate receptor is reversibly palmitoylated and required for normal trafficking and lysosomal enzyme sorting.

Cysteine34 of the cytoplasmic tail of the cation-dependent mannose 6-phosphate receptor is reversibly palmitoylated and required for normal trafficking and lysosomal enzyme sorting.

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

In vitro reconstitution of substrate S-acylation by the zDHHC family of protein acyltransferases

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