Fatty Acylation of Proteins

Schultz, Alan M.; Henderson, Louis E.; Oroszlan, Stephen

doi:10.1146/annurev.cb.04.110188.003143

Cited by 234 publications

(144 citation statements)

References 187 publications

Supporting

Mentioning

141

Contrasting

Order By: Relevance

“…The first ten amino acids at the N-terminus, which are identical in 43 kDa protein from all three species, include a sequence appropriate for myristylation. The 43 kDa protein from Torpedo electric organ [29] and that from BC3H-1 muscle ceils [27] have been shown to be myristylated, a feature often involved in the association of proteins with membranes (review [32]). However, not all myristylated proteins are membrane bound and myristylation in some cases is not sufficient for association with the lipid bilayer [32].…”

Section: Northern Blot Analysismentioning

confidence: 99%

“…The 43 kDa protein from Torpedo electric organ [29] and that from BC3H-1 muscle ceils [27] have been shown to be myristylated, a feature often involved in the association of proteins with membranes (review [32]). However, not all myristylated proteins are membrane bound and myristylation in some cases is not sufficient for association with the lipid bilayer [32]. In addition, structural studies of the N-myristylated picornavirus capsid protein VP4 have shown that the fatty acid resides in a hydrophobic pocket formed by amino acid side chains [33].…”

Section: Northern Blot Analysismentioning

confidence: 99%

See 1 more Smart Citation

Expression of RNA transcripts for the postsynaptic 43 kDa protein in innervated and denervated rat skeletal muscle

Froehner

1989

FEBS Letters

View full text Add to dashboard Cite

A cDNA clone encoding the mouse muscle postsynaptic 43 kDa protein was isolated and sequenced. The amino acid sequence of this protein, which is closely associated with nicotinic acetylcholine receptors at Torpedo electrocyte and vertebrate skeletal muscle synapses, is very similar in different species. A cysteine-rich region homologous to part of the regulatory domain of protein kinase C may be important in interactions of this protein with the lipid bilayer. RNA transcripts for the 43 kDa protein increase only 2-3-fold after denervation of rat skeletal muscle, in sharp contrast to the a-subunit of the muscle nicotinic receptor which increases more than 30-fold. Thus, the expression of these two proteins is regulated by different mechanisms.

show abstract

Section: Northern Blot Analysismentioning

confidence: 99%

Section: Northern Blot Analysismentioning

confidence: 99%

Expression of RNA transcripts for the postsynaptic 43 kDa protein in innervated and denervated rat skeletal muscle

Froehner

1989

FEBS Letters

View full text Add to dashboard Cite

show abstract

“…One of the strategies to anchor a protein at the lipid membrane is covalent modification of proteins by fatty acids or other lipids. All bacteria rely on acylation of N-terminal Cys residues of lipoproteins to allow tight anchorage on the membrane surface (1). This uniquely bacterial modification was first observed in 1969 in a major outer membrane protein of Escherichia coli called Braun's lipoprotein and later detected in every bacterial organism studied (2).…”

mentioning

confidence: 99%

The Acylation State of Surface Lipoproteins of Mollicute Acholeplasma laidlawii

Serebryakova

Demina

Galyamina

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Acylation of the N-terminal Cys residue is an essential, ubiquitous, and uniquely bacterial posttranslational modification that allows anchoring of proteins to the lipid membrane. In Gram-negative bacteria, acylation proceeds through three sequential steps requiring lipoprotein diacylglyceryltransferase, lipoprotein signal peptidase, and finally lipoprotein N-acyltransferase. The apparent lack of genes coding for recognizable homologs of lipoprotein N-acyltransferase in Gram-positive bacteria and Mollicutes suggests that the final step of the protein acylation process may be absent in these organisms. In this work, we monitored the acylation state of eight major lipoproteins of the mollicute Acholeplasma laidlawii using a combination of standard two-dimensional gel electrophoresis protein separation, blotting to nitrocellulose membranes, and MALDI-MS identification of modified N-terminal tryptic peptides. We show that for each A. laidlawii lipoprotein studied a third fatty acid in an amide linkage on the N-terminal Cys residue is present, whereas diacylated species were not detected. The result thus proves that A. laidlawii encodes a lipoprotein N-acyltransferase activity. We hypothesize that N-acyltransferases encoded by genes non-homologous to N-acyltransferases of Gram-negative bacteria are also present in other mollicutes and Gram-positive bacteria.Essential cellular activities such as transport, sensing, signal transduction, growth, adhesion, and pathogenesis require proteins localized on the cell surface. One of the strategies to anchor a protein at the lipid membrane is covalent modification of proteins by fatty acids or other lipids. All bacteria rely on acylation of N-terminal Cys residues of lipoproteins to allow tight anchorage on the membrane surface (1). This uniquely bacterial modification was first observed in 1969 in a major outer membrane protein of Escherichia coli called Braun's lipoprotein and later detected in every bacterial organism studied (2). Adhesion proteins and substrate-binding subunits of ATPbinding cassette (ABC) 2 transporters are known to be attached to the membrane in this manner. Thousands of proteins predicted to be lipoproteins "by similarity" according to the presence of consensus sequences of Sec Type II or Tat Type II signal peptides are also thought to be acylated (3).Bacteria of the Mollicutes class are widespread in nature and are characterized by the lack of a rigid cell wall and drastically reduced genome sizes. In fact, representatives of this class are the simplest self-replicating organisms able to independently subsist, generate energy, and adapt to changing environments (4 and references therein). Most mollicutes depend on cholesterol and are partially or totally incapable of fatty acid synthesis and therefore depend on the host or the culture medium for a constant supply of these substances (5). Acholeplasma laidlawii is a convenient model mollicute because of its relatively simple nutritional requirements and fast growth rate. A. laidlawii can synthesize limit...

show abstract

“…The role of N-terminal myristoylation is to regulate among other things protein function and protein anchoring to the internal leaflet of the plasma membrane (5). A much less studied and less frequent type of myristoylation takes place at internal amino acid residues via ester or amide bonds (7)(8)(9)(10); it has been estimated that 0.09-0.24% of total cell protein binds to myristate using this mechanism (11). Internal myristoylation has been reported for a few mammalian proteins such as the β-subunit of the insulin receptor, the precursor of interleukin 1α, and tumor necrosis factor α (8-10).…”

mentioning

confidence: 99%

Unconventional myristoylation of large-conductance Ca ²⁺ -activated K ⁺ channel (Slo1) via serine/threonine residues regulates channel surface expression

Alioua

Li²,

Wu³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Protein myristoylation is a means by which cells anchor proteins into membranes. The most common type of myristoylation occurs at an N-terminal glycine. However, myristoylation rarely occurs at an internal amino acid residue. Here we tested whether the α-subunit of the human large-conductance voltage-and Ca 2+ -activated K + channel (hSlo1) might undergo internal myristoylation. hSlo1 expressed in HEK293T cells incorporated [ 3 H]myristic acid via a posttranslational mechanism, which is insensitive to cycloheximide, an inhibitor of protein biosynthesis. In-gel hydrolysis of [ 3 H]myristoyl-hSlo1 with alkaline NH 2 OH (which cleaves hydroxyesters) but not neutral NH 2 OH (which cleaves thioesters) completely removed [ 3 H]myristate from hSlo1, suggesting the involvement of a hydroxyester bond between hSlo1's hydroxyl-bearing serine, threonine, and/or tyrosine residues and myristic acid; this type of esterification was further confirmed by its resistance to alkaline Tris·HCl. Treatment of cells expressing hSlo1 with 100 μM myristic acid caused alteration of hSlo1 activation kinetics and a 40% decrease in hSlo1 current density from 20 to 12 nA*MΩ. Immunocytochemistry confirmed a decrease in hSlo1 plasmalemma localization by myristic acid. Replacement of the six serines or the seven threonines (but not of the single tyrosine) of hSlo1 intracellular loops 1 and 3 with alanines decreased hSlo1 direct myristoylation by 40-44%, whereas in combination decreased myristoylation by nearly 90% and abolished the myristic acid-induced change in current density. Our data demonstrate that an ion channel, hSlo1, is internally and posttranslationally myristoylated. Myristoylation occurs mainly at hSlo1 intracellular loop 1 or 3, and is an additional mechanism for channel surface expression regulation.MaxiK channel | BK Ca channel | posttranslational modification | traffic T he large-conductance voltage-and calcium-activated potassium channel (MaxiK, BK Ca ) is ubiquitously expressed regulating numerous physiological functions such as neuronal action potential firing, neurotransmitter release, and vascular smooth muscle tone (1). Four pore-forming α-subunits (Slo1, an ∼125-kDa protein) make a functional MaxiK channel. Based on structure/function studies, Slo1 protein can be separated into two main functional cassettes: the multipass transmembranous N terminus (∼40 kDa) and a large cytoplasmic C terminus (∼85 kDa). The N terminus has seven (S0-S6) transmembrane segments, together forming the voltage-sensing and the pore-conducting domains. The intracellular C terminus carries two RCK domains (RCK1, RCK2) and contains the Ca 2+

show abstract

Fatty Acylation of Proteins

Cited by 234 publications

References 187 publications

Expression of RNA transcripts for the postsynaptic 43 kDa protein in innervated and denervated rat skeletal muscle

Expression of RNA transcripts for the postsynaptic 43 kDa protein in innervated and denervated rat skeletal muscle

The Acylation State of Surface Lipoproteins of Mollicute Acholeplasma laidlawii

Unconventional myristoylation of large-conductance Ca ²⁺ -activated K ⁺ channel (Slo1) via serine/threonine residues regulates channel surface expression

Contact Info

Product

Resources

About

Fatty Acylation of Proteins

Cited by 234 publications

References 187 publications

Expression of RNA transcripts for the postsynaptic 43 kDa protein in innervated and denervated rat skeletal muscle

Expression of RNA transcripts for the postsynaptic 43 kDa protein in innervated and denervated rat skeletal muscle

The Acylation State of Surface Lipoproteins of Mollicute Acholeplasma laidlawii

Unconventional myristoylation of large-conductance Ca 2+ -activated K + channel (Slo1) via serine/threonine residues regulates channel surface expression

Contact Info

Product

Resources

About

Unconventional myristoylation of large-conductance Ca ²⁺ -activated K ⁺ channel (Slo1) via serine/threonine residues regulates channel surface expression