Technologies and Challenges in Proteomic Analysis of Protein S-acylation.

Bo Zhou

doi:10.4172/jpb.1000327

Abstract

Protein S-acylation (also called palmitoylation) is a pervasive post-translational modification that plays critical roles in regulating protein trafficking, localization, stability, activity, and complex formation. The past decade has witnessed tremendous advances in the study of protein S-acylation, largely owing to the development of novel S-acylproteomics technologies. In this review, we summarize current S-acylproteomics approaches, critically review published S-acylproteomics studies, and envision future directions for the burgeoning S-acylproteomics field. Emerging S-acylproteomics technologies promise to shed new light on this distinct post-translational modification and facilitate the discovery of new disease mechanisms, biomarkers, and therapeutic targets.

Highlights

Protein S-acylation is the post-translational addition of long chain fatty acids to specific cysteines of proteins via labile thioester bonds [1]
Since the vast majority of S-acylated proteins are modified with palmitate (16:0) [2], S-acylation is more commonly called Spalmitoylation or palmitoylation
The study of protein S-acylation is greatly accelerated by the development of acyl-biotinyl exchange (ABE) and MLCC methods as well as their derivatives for the purification of S-acylated proteins or peptides

Summary

Introduction

Protein S-acylation is the post-translational addition of long chain fatty acids to specific cysteines of proteins via labile thioester bonds [1]. S-acylation was first reported in 1979 [6], four months earlier than the discovery of tyrosine phosphorylation [7]. After over three decades, the study of protein S-acylation lags far behind that of protein phosphorylation, largely due to a lack of robust methods for sensitive detection and analysis of S-acylation. Unlike phosphorylation and many other post-translational modifications, S-acylation is nonantigenic, so no anti-S-acylated cysteine antibody has ever been successfully produced. The past decade has witnessed tremendous advances in studying protein S-acylation, mostly owing to 1) the discovery of S-acylation and de-S-acylation enzymes, 2) the development of biochemical methods to selectively enrich S-acylated proteins and/or peptides, and 3) the rapid development of mass spectrometry (MS)-based proteomics

Methods

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Conclusion