Difference Between Acylation and Prenylation

The key difference between acylation and prenylation is that acylation refers to the covalent attachment of fatty acids to proteins, while prenylation refers to the covalent attachment of prenyl groups to proteins.

Post-translational modifications are a type of protein modification that happens after the initial synthesis of proteins. There are several types of mechanisms. Acylation and prenylation are two types in which covalent attachment of lipid groups modifies proteins in order to associate with membranes, both intracellularly and extracellularly. In prenylation, prenyl groups such as a farnesyl or geranylgeranyl are added to proteins. In acylation, fatty acids are covalently attached to proteins. Acylation and prenylation happen in many proteins in eukaryotic cells. As a result, modified proteins regulate numerous biological pathways, such as membrane trafficking, protein secretion, signal transduction, and apoptosis.

CONTENTS

1. Overview and Key Difference
2. What is Acylation 
3. What is Prenylation
4. Similarities Between Acylation and Prenylation
5. Side by Side Comparison – Acylation vs Prenylation in Tabular Form
6. Summary

What is Acylation?

Acylation is the covalent attachment of fatty acids to proteins. It is a post-translational modification. In acylation, the linkage type and the species of fatty acid can be different. Based on that, there are two categories of acylation as N-terminal myristoylation (N-acylation) and palmitoylation (S-acylation).

N-acylation or N terminal myristoylation is the attachment of myristate, which is a 14 carbon saturated fatty acid to N terminal glycine residue via an amide linkage. It is an irreversible process. S-acylation or palmitoylation, on the other hand, is the covalent attachment of palmitic acid, which is a long-chain saturated fatty acid to cysteine residue via a thioester linkage. Palmitoylation is a reversible post-translational protein modification. Fatty acylation regulates intracellular trafficking, subcellular localization, protein-protein and protein-lipid interactions.

What is Prenylation?

Prenylation is a post-translational modification of proteins. It involves the addition of a hydrophobic group to a protein. Generally, two types of prenyl groups, either a farnesyl or a geranylgeranyl moiety, is added to C-terminal cysteine of the target protein. Three enzymes catalyze prenylation in cells. They are farnesyl transferase, Caax protease and geranylgeranyl transferase.

Protein prenylation occurs through three steps, starting from the attachment of the isoprenoid followed by proteolysis and methyl esterification of the C-terminal prenylated cysteine. Prenylation is an important process to mediate protein-protein interactions and protein-membrane interactions.

What are the Similarities Between Acylation and Prenylation?

• Acylation and prenylation are two types of post-translational modifications.
• Both processes do hydrophobic modifications to proteins.

What is the Difference Between Acylation and Prenylation?

Acylation is the covalent attachment of myristate fatty acids to N terminal glycine residue and palmitic acid to a cysteine residue of a protein via amide linkage and thioester linkage, respectively. Prenylation is the covalent attachment of farnesyl or geranylgeranyl to a cysteine at or near the carboxy-terminal of specific proteins via a thioether bond.  So, this is the key difference between acylation and prenylation.

Below infographic tabulates more differences between acylation and prenylation.

Summary – Acylation vs Prenylation

Acylation and prenylation are two post-translational protein modifications. Acylation is the covalent attachment of fatty acids to proteins. Prenylation is the addition of prenyl groups to proteins. Both fatty acids and prenyl groups are hydrophobic modifiers of proteins. In acylation, myristate and palmitate represent the most common fatty acid modifying groups. In prenylation, farnesyl or geranylgeranyl groups act as the modifiers. Fatty acylation regulates intracellular trafficking, subcellular localization, protein-protein and protein-lipid interactions. Prenylation is an important process to mediate protein-protein interactions and protein-membrane interactions. Thus, this is the summary of the difference between acylation and prenylation.

Reference:

1. Veit, Michael, and Michael F.G. Schmidt. “Fatty Acid Acylation of Proteins.” SpringerLink, Springer, Berlin, Heidelberg, 1 Jan. 1970, Available here.
2. Palsuledesai, Charuta C., and Mark D. Distefano. “Protein Prenylation: Enzymes, Therapeutics, And Biotechnology Applications”. ACS Chemical Biology, vol 10, no. 1, 2014, pp. 51-62. American Chemical Society (ACS), doi:10.1021/cb500791f. Accessed 30 Sept 2020.

Image Courtesy:

1. “Benzen acylowany” By Arrowsmaster – Own work (Public Domain) via Commons Wikimedia

2. “Prenyl group” By Katanac (talk) (Uploads) – (Original text: Katanac (talk) (Uploads)-(GFDL) via Commons Wikimedia