The physiology of protein S-acylation

Chamberlain, Luke H. and Shipston, Michael J. (2015) The physiology of protein S-acylation. Physiological Reviews, 95 (2). pp. 341-376. ISSN 1522-1210 (https://doi.org/10.1152/physrev.00032.2014)

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Abstract

Protein S-acylation, the only fully reversible posttranslational lipid modification of proteins, is emerging as a ubiquitous mechanism to control the properties and function of a diverse array of proteins and consequently physiological processes. S-acylation results from the enzymatic addition of long-chain lipids, most typically palmitate, onto intracellular cysteine residues of soluble and transmembrane proteins via a labile thioester linkage. Addition of lipid results in increases in protein hydrophobicity that can impact on protein structure, assembly, maturation, trafficking, and function. The recent explosion in global S-acylation (palmitoyl) proteomic profiling as a result of improved biochemical tools to assay S-acylation, in conjunction with the recent identification of enzymes that control protein S-acylation and de-acylation, has opened a new vista into the physiological function of S-acylation. This review introduces key features of S-acylation and tools to interrogate this process, and highlights the eclectic array of proteins regulated including membrane receptors, ion channels and transporters, enzymes and kinases, signaling adapters and chaperones, cell adhesion, and structural proteins. We highlight recent findings correlating disruption of S-acylation to pathophysiology and disease and discuss some of the major challenges and opportunities in this rapidly expanding field.

ORCID iDs

Chamberlain, Luke H. ORCID logoORCID: https://orcid.org/0000-0002-8701-4995 and Shipston, Michael J.;
CORE (COnnecting REpositories)