Protein Acylation

Types of Protein Acylation

Protein acylation can occur through different mechanisms, both enzymatic and non-enzymatic. Enzymatic acylation is the more common type and involves the action of specific enzymes known as acyltransferases. These enzymes transfer acyl groups from donor molecules, such as acyl-CoA, to specific amino acid residues on target proteins. The acyl groups can vary in structure, including acetyl, succinyl, malonyl, crotonyl, β-hydroxybutyryl, lactyl, myristoyl, and palmitoyl. Each type of acylation imparts distinct chemical properties to the modified protein, influencing its function and localization within the cell.

Acetylation

Acetylation involves the addition of an acetyl group (-COCH3) to the ε-amino group of lysine residues. This modification is dynamically regulated by acetyltransferases (HATs) and deacetylases (HDACs). Acetylation influences protein stability, DNA-binding affinity, and protein-protein interactions, thereby affecting cellular processes such as gene expression, cell cycle regulation, and signal transduction.

Succinylation

Succinylation refers to the addition of a succinyl group (-CO-CH2-CH2-CO2H) to lysine residues. Succinylation is carried out by a group of different enzymes, including sirtuin deacetylases (SIRTs) and succinyltransfers. This modification has been implicated in cellular metabolism, particularly in the regulation of mitochondrial function and energy production. Succinylation can affect protein stability, enzymatic activity, and protein-protein interactions.

Malonylation

Protein malonylation refers to the process of covalently binding a malonyl group (such as malonyl-CoA and other donors) to the lysine residue of the substrate protein under the catalysis of an enzyme. This process is reversible. Malonylation plays an important role in metabolic processes, especially energy metabolism and photosynthesis, and can affect fatty acid synthesis, mitochondrial respiration, glycolysis, inflammatory response, etc.

Crotonylation

Protein crotonylation exists in core histones and some non-histone proteins of a variety of organisms. Similar to other types of PTM, protein crotonylation is a reversible modification with important functions such as the promotion of gene expression and regulation. Among crotonylations, the most common one is lysine crotonylation.

β-Hydroxybutyrylation

β-Hydroxybutyrylation is a recently discovered PTM that involves the addition of a β-hydroxybutyryl group to lysine residues in proteins. This modification has been linked to cellular metabolism, particularly in the context of ketone body utilization during fasting or ketogenic diets. β-Hydroxybutyrylation can influence protein-protein interactions and regulate protein function.

Lactylation

Lactoylation, a novel PTM, is a novel contributor to the epigenetic landscape. It controls diverse physiological and pathological contexts through integrated mechanisms. Recently, protein lactylation has been reported to play a critical role in regulating complex biological functions, including inflammation, neoplastic diseases, fibrosis, Alzheimer's disease (AD), embryonic development, stemness maintenance, and neuromodulation.

Myristoylation

Myristoylation involves the attachment of a 14-carbon unsaturated fatty acid, myristic acid, to the N-terminal glycine residue of proteins. This lipid modification facilitates the association of proteins with cellular membranes, enabling their proper localization and functioning. Myristoylation is crucial for the membrane anchoring of various signaling proteins.

Palmitoylation

Palmitoylation is the covalent connection between fatty acids (such as palmitic acid) and cysteine, while the covalent connection frequency with serine and threonine residues of proteins is relatively low, and proteins are usually membrane proteins. This reversible modification is executed by palmitoyl acyltransferases (PATs) and depalmitoylating enzymes. This lipid modification is involved in membrane targeting, protein trafficking, and modulating protein-protein interactions. It is particularly important for the localization and function of peripheral membrane proteins.