Identification of a Novel Sequence Motif Recognized by the Ankyrin Repeat Domain of zDHHC17/13 S-Acyltransferases

Lemonidis, Kimon; Sanchez-Perez, Maria C.; Chamberlain, Luke H.

doi:10.1074/jbc.m115.657668

Cited by 77 publications

(117 citation statements)

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“…The consensus sequences for other lipidations such as myristoylation and isoprenylation were already identified as glycine in the Nterminal MGXXXS/T (M, Met; G, Gly; S, Ser; T, Thr; X, any amino acid) for myristoylation and cysteine in the C-terminal CAAX motif (C, Cys; A, an aliphatic amino acid; X, any amino acid) for isoprenylation [49]. Regarding the consensus sequence for palmitoylation, a very recent report identified a novel sequence motif that is recognized by the ankyrin repeat domain of DHHC17 and DHHC13, which is the first demonstration of a motif as consensus sequences of substrates recognized by ankyrin repeat-containing DHHCs [50]. A number of DHHC17 substrates and DHHC17-and DHHC13-interacting palmitoylated proteins, including SNAP-25b, SNAP-23, CSP, huntingtin, cytoplasmic linker protein 3 (CLIP3), and microtubule associated protein 6 (MAP6) contain a ΨβXXQP (Ψ, an aliphatic amino acid; β, a C-β branched amino acid Val, Ile, or Thr; X, any amino acid; Q, Gln; P, Pro) motif.…”

Section: Substrate Specificitymentioning

confidence: 99%

“…A number of DHHC17 substrates and DHHC17-and DHHC13-interacting palmitoylated proteins, including SNAP-25b, SNAP-23, CSP, huntingtin, cytoplasmic linker protein 3 (CLIP3), and microtubule associated protein 6 (MAP6) contain a ΨβXXQP (Ψ, an aliphatic amino acid; β, a C-β branched amino acid Val, Ile, or Thr; X, any amino acid; Q, Gln; P, Pro) motif. The consensus sequence was recognized by DHHC17 and DHHC13 via the ankyrin repeats domain in their cytosolic Nterminus [50]. The consensus sequences for the recognition by and catalytic activity of most DHHC proteins will need to be identified.…”

Section: Substrate Specificitymentioning

confidence: 99%

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Palmitoylation in Alzheimer⿿s disease and other neurodegenerative diseases

Cho

Park

2016

Pharmacological Research

110

108

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Posttranslational modifications of proteins are important regulatory processes endowing the proteins functional complexity. Over the last decade, numerous studies have shed light on the roles of palmitoylation, one of the most common lipid modifications, in various aspects of neuronal functions. Major players regulating palmitoylation are the enzymes that mediate palmitoylation and depalmitoylation which are palmitoyl acyltransferases (PATs) and protein thioesterases, respectively. In this review, we will provide and discuss current understandings on palmitoyation/depalmitoylation control mediated by PATs and/or protein thioesterases for neuronal functions in general and also for Alzheimer's disease in particular, and other neurodegenerative diseases such as Huntington's disease, schizophrenia and intellectual disability.

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Section: Substrate Specificitymentioning

confidence: 99%

Section: Substrate Specificitymentioning

confidence: 99%

Palmitoylation in Alzheimer⿿s disease and other neurodegenerative diseases

Cho

Park

2016

Pharmacological Research

110

108

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“…Usually two AR containing DHHC PATs are found in per genome, such as in mammals (Fukata et al, 2004), yeast (Roth et al, 2006), fly (Bannan et al, 2008), apicomplexan parasite (Frénal et al, 2013), nematode (Edmonds and Morgan, 2014), and plants (Yuan et al, 2013). It is thought that AR can help these PAT to recognize its specific targets for S-acylation (Lemonidis et al, 2015). However, other functions of AR that are independent from S-acylation were also found in some such PATs (Harada et al, 2003; Hemsley and Grierson, 2011; Yang and Cynader, 2011).…”

Section: Protein S-acyl Transferases (Pats)mentioning

confidence: 99%

Progress toward Understanding Protein S-acylation: Prospective in Plants

2017

Front. Plant Sci.

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S-acylation, also known as S-palmitoylation or palmitoylation, is a reversible post-translational lipid modification in which long chain fatty acid, usually the 16-carbon palmitate, covalently attaches to a cysteine residue(s) throughout the protein via a thioester bond. It is involved in an array of important biological processes during growth and development, reproduction and stress responses in plant. S-acylation is a ubiquitous mechanism in eukaryotes catalyzed by a family of enzymes called Protein S-Acyl Transferases (PATs). Since the discovery of the first PAT in yeast in 2002 research in S-acylation has accelerated in the mammalian system and followed by in plant. However, it is still a difficult field to study due to the large number of PATs and even larger number of putative S-acylated substrate proteins they modify in each genome. This is coupled with drawbacks in the techniques used to study S-acylation, leading to the slower progress in this field compared to protein phosphorylation, for example. In this review we will summarize the discoveries made so far based on knowledge learnt from the characterization of protein S-acyltransferases and the S-acylated proteins, the interaction mechanisms between PAT and its specific substrate protein(s) in yeast and mammals. Research in protein S-acylation and PATs in plants will also be covered although this area is currently less well studied in yeast and mammalian systems.

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“…A recent report highlights the important role of DHHC-ANK domains in the recognition of the substrate sequence. 36 The new substrate consensus sequence recognized by the DHHC17 and 13 ANK domains was detected in several proteins including, among others, SNAP25, SNAP23, and huntingtin. 36 Similarly, it was shown that the PDZ domain of DHHC5 binds glutamate receptor interacting protein (GRIP1b), facilitating the palmitoylation of GRIP1 band its subsequent trafficking to its dendritic localization.…”

Section: Zdhhc Proteins: Substrate-specificitymentioning

confidence: 99%

“…36 The new substrate consensus sequence recognized by the DHHC17 and 13 ANK domains was detected in several proteins including, among others, SNAP25, SNAP23, and huntingtin. 36 Similarly, it was shown that the PDZ domain of DHHC5 binds glutamate receptor interacting protein (GRIP1b), facilitating the palmitoylation of GRIP1 band its subsequent trafficking to its dendritic localization. 37 PDZ-mediated interactions between DHHC5 and neuronal PSD-95 protein was previously shown 38 and, in a separate study, a mutant of DHHC5 with a deletion of the PDZ domain (DHHC5 ÁPDZb) could not bind to PSD-95.…”

Section: Zdhhc Proteins: Substrate-specificitymentioning

confidence: 99%

Protein palmitoylation: Palmitoyltransferases and their specificity

Tabaczar

Czogalla

Podkalicka

et al. 2017

Exp Biol Med (Maywood)

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Protein palmitoylation is one of most important reversible post-translational modifications of protein function in cellsignaling systems. This review gathers the latest information on the molecular mechanism of protein palmitoyl transferase action. It also discusses the issue of substrate specificity of palmitoyl transferases. Another important question is the role of depalmitoylation enzymes. This review should help to formulate questions concerning the regulation of activity of particular PATs as well as of depalmitoylating enzymes (APT). AbstractA plethora of novel information has emerged over the past decade regarding protein lipidation. The reversible attachment of palmitic acid to cysteine residues, termed S-palmitoylation, has focused a special attention. This is mainly due to the unique role of this modification in the regulation of protein trafficking and function. A large family of protein acyltransferases (PATs) containing a conserved aspartate-histidine-histidine-cysteine motif use ping-pong kinetic mechanism to catalyze S-palmitoylation of a substrate protein. Here, we discuss the topology of PAT proteins and their cellular localization. We will also give an overview of the mechanism of protein palmitoylation and how it is regulated. New information concerning the recent discovery of depalmitoylating enzymes belonging to the family of a/b-hydrolase domain-containing protein 17 (ABHD17A) is included. Considering the recent advances that have occurred in understanding the mechanisms underlying the interplay between palmitoylation and depalmitoylation, it is clear that we are beginning to understand the fundamental nature of how cellular signal-transduction mediates membrane-level organization in health and disease.

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Identification of a Novel Sequence Motif Recognized by the Ankyrin Repeat Domain of zDHHC17/13 S-Acyltransferases

Cited by 77 publications

References 74 publications

Palmitoylation in Alzheimer⿿s disease and other neurodegenerative diseases

Palmitoylation in Alzheimer⿿s disease and other neurodegenerative diseases

Progress toward Understanding Protein S-acylation: Prospective in Plants

Protein palmitoylation: Palmitoyltransferases and their specificity

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