Site-specific chemical fatty-acylation for gain-of-function analysis of protein <i>S</i>-palmitoylation in live cells

Li, Yumeng; Wang, Shushu; Chen, Yanchi; Li, Manjia; Dong, Xiaoshu; Hang, Howard C.; Peng, Tao

doi:10.1039/d0cc06073a

Cited by 24 publications

(26 citation statements)

References 38 publications

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“…In the future we anticipate the development of novel chemical tools with specific utility in studying highly dynamic and transient acylation/deacylation cycles. As an example, a new methodology for site-specific incorporation of lipids at cycloalkyne-conjugated unnatural amino acids was recently described which should facilitate understanding the attachment of specific lipids at defined sites "on demand" (Li et al, 2020). We have a nascent understanding of the functional outcomes of the attachment of lipids other than the 16-carbon saturated fatty acid palmitic acid.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Dynamic Protein S-Acylation

Chen

Fan

Boehning

2021

Front. Mol. Biosci.

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Protein S-acylation is the reversible addition of fatty acids to the cysteine residues of target proteins. It regulates multiple aspects of protein function, including the localization to membranes, intracellular trafficking, protein interactions, protein stability, and protein conformation. This process is regulated by palmitoyl acyltransferases that have the conserved amino acid sequence DHHC at their active site. Although they have conserved catalytic cores, DHHC enzymes vary in their protein substrate selection, lipid substrate preference, and regulatory mechanisms. Alterations in DHHC enzyme function are associated with many human diseases, including cancers and neurological conditions. The removal of fatty acids from acylated cysteine residues is catalyzed by acyl protein thioesterases. Notably, S-acylation is now known to be a highly dynamic process, and plays crucial roles in signaling transduction in various cell types. In this review, we will explore the recent findings on protein S-acylation, the enzymatic regulation of this process, and discuss examples of dynamic S-acylation.

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Section: Discussionmentioning

confidence: 99%

Regulation of Dynamic Protein S-Acylation

Chen

Fan

Boehning

2021

Front. Mol. Biosci.

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“…We first attempted to improve the incorporation efficiency by overexpression of an engineered eukaryotic release factor 1 (eRF1). With an E55D point mutation, this engineered eRF1 was shown to improve amber suppression by Pyl tRNA CUA(U25C) ( Li et al., 2020 ; Schmied et al., 2014 ). We therefore tested the incorporation efficiency of both aaRS/tRNA pairs here in the presence and absence of this engineered eRF1; however, no significant improvement was observed in either case ( Figure S2 D).…”

Section: Resultsmentioning

confidence: 99%

Development of mammalian cell logic gates controlled by unnatural amino acids

Mills

Barlow

Jones

et al. 2021

Cell Reports Methods

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“…Similarly, identifying and disrupting the depalmitoylase also produces results consistent with the mutation of palmitoylated Cys. Recently, a method using amber suppression technology and click chemistry to insert a palmitoyl cysteine mimic on proteins in live HEK293T cells has been reported[ 20 ]. This method may allow for the gain-of-function analysis of S-palmitoylation.…”

Section: Overview Of Protein Cysteine Palmitoylationmentioning

confidence: 99%

Palmitoylation in Crohn’s disease: Current status and future directions

Cheng¹,

Ren²,

Lu³

et al. 2021

WJG

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S-palmitoylation is one of the most common post-translational modifications in nature; however, its importance has been overlooked for decades. Crohn’s disease (CD), a subtype of inflammatory bowel disease (IBD), is an autoimmune disease characterized by chronic inflammation involving the entire gastrointestinal tract. Bowel damage and subsequent disabilities caused by CD are a growing global health issue. Well-acknowledged risk factors for CD include genetic susceptibility, environmental factors, such as a westernized lifestyle, and altered gut microbiota. However, the pathophysiological mechanisms of this disorder are not yet comprehensively understood. With the rapidly increasing global prevalence of CD and the evident role of S-palmitoylation in CD, as recently reported, there is a need to investigate the relationship between CD and S-palmitoylation. In this review, we summarize the concept, detection, and function of S-palmitoylation as well as its potential effects on CD, and provide novel insights into the pathogenesis and treatment of CD.

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Site-specific chemical fatty-acylation for gain-of-function analysis of protein S-palmitoylation in live cells

Abstract: Protein S-palmitoylation, or S-fatty-acylation, regulates many fundamental cellular processes in eukaryotes. Herein, we present a chemical fatty-acylation approach that involves site-specific incorporation of cycloalkyne-containing unnatural amino acids and subsequent bioorthogonal...

Cited by 24 publications

References 38 publications

Regulation of Dynamic Protein S-Acylation

Regulation of Dynamic Protein S-Acylation

Development of mammalian cell logic gates controlled by unnatural amino acids

Palmitoylation in Crohn’s disease: Current status and future directions

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