Myristoylation vs. Palmitoylation

Attribute	Myristoylation	Palmitoylation
Definition	Covalent attachment of a myristic acid to an N-terminal glycine residue of a protein	Covalent attachment of a palmitic acid to cysteine residues of a protein
Lipid	Myristic acid	Palmitic acid
Attachment site	N-terminal glycine residue	Cysteine residues
Attachment type	Amide bond	Thioester bond
Role	Targeting protein to cellular membranes	Regulating protein localization and function
Reversibility	Irreversible	Reversible
Enzyme	N-myristoyltransferase (NMT)	Palmitoyl acyltransferases (PATs)

Introduction

Post-translational modifications (PTMs) play a crucial role in regulating protein function and localization within cells. Two common lipid modifications that occur on proteins are myristoylation and palmitoylation. These modifications involve the attachment of fatty acids to specific amino acids, resulting in the addition of hydrophobic moieties to the protein. While both myristoylation and palmitoylation serve similar purposes, they differ in terms of the lipid attached, the target amino acids, and the functional consequences. In this article, we will explore the attributes of myristoylation and palmitoylation in detail.

Myristoylation

Myristoylation is a PTM that involves the covalent attachment of a 14-carbon saturated fatty acid called myristic acid to the N-terminal glycine residue of a protein. This modification is catalyzed by the enzyme N-myristoyltransferase (NMT) and occurs co-translationally, meaning it takes place during protein synthesis. Myristoylation is a reversible modification, and the myristoyl group can be removed by the action of specific enzymes called myristoyl-protein thioesterases.

One of the key features of myristoylation is its role in protein membrane targeting. The addition of the myristoyl group enhances the hydrophobicity of the protein, facilitating its association with cellular membranes. Myristoylation is commonly found in proteins that are involved in signal transduction pathways, such as G proteins and kinases. The myristoyl group acts as a membrane anchor, allowing these proteins to interact with specific membrane components and carry out their functions.

Furthermore, myristoylation can also influence protein-protein interactions. The myristoyl group can serve as a binding site for other proteins or domains, promoting the formation of protein complexes. This interaction can be crucial for the proper functioning of signaling cascades and the assembly of multiprotein complexes.

It is important to note that myristoylation is a highly conserved modification, meaning that the target glycine residue is present in a wide range of organisms, from bacteria to humans. This conservation highlights the significance of myristoylation in cellular processes and suggests its evolutionary advantage.

Palmitoylation

Palmitoylation, on the other hand, involves the attachment of a 16-carbon saturated fatty acid called palmitic acid to cysteine residues within a protein. Unlike myristoylation, palmitoylation can occur on both N-terminal and internal cysteine residues. This modification is catalyzed by a family of enzymes called palmitoyl acyltransferases (PATs) and is reversible through the action of palmitoyl-protein thioesterases.

Similar to myristoylation, palmitoylation plays a crucial role in protein membrane targeting. The addition of the palmitoyl group increases the hydrophobicity of the protein, facilitating its association with cellular membranes. Palmitoylation is commonly found in proteins that are involved in synaptic transmission, such as neurotransmitter receptors and signaling molecules. The palmitoyl group allows these proteins to localize to specific membrane compartments, such as the postsynaptic density, where they can interact with other synaptic proteins.

In addition to membrane targeting, palmitoylation also regulates protein stability and trafficking. Palmitoylation can influence protein-protein interactions, leading to the formation of protein complexes or the recruitment of specific proteins to distinct cellular compartments. Furthermore, palmitoylation can modulate protein turnover by affecting protein degradation pathways.

Unlike myristoylation, palmitoylation is a more dynamic modification. The reversible nature of palmitoylation allows for rapid and precise regulation of protein localization and function. This flexibility is particularly important in processes that require rapid changes, such as synaptic plasticity and cellular signaling.

Comparison

While myristoylation and palmitoylation share some similarities, such as their role in protein membrane targeting and reversible nature, there are several key differences between these two lipid modifications.

• Lipid Attachment: Myristoylation involves the attachment of a 14-carbon myristic acid to the N-terminal glycine, whereas palmitoylation involves the attachment of a 16-carbon palmitic acid to cysteine residues.
• Target Amino Acids: Myristoylation specifically targets the N-terminal glycine, while palmitoylation can occur on both N-terminal and internal cysteine residues.
• Enzymes: Myristoylation is catalyzed by N-myristoyltransferase (NMT), while palmitoylation is catalyzed by palmitoyl acyltransferases (PATs).
• Conservation: Myristoylation is highly conserved across different organisms, while palmitoylation shows more variability in terms of target proteins and sites.
• Functional Consequences: Myristoylation is often involved in signal transduction pathways and protein-protein interactions, while palmitoylation is commonly associated with synaptic transmission and protein stability/trafficking.

Conclusion

Myristoylation and palmitoylation are two important lipid modifications that play crucial roles in protein function and localization. While myristoylation involves the attachment of a 14-carbon myristic acid to the N-terminal glycine, palmitoylation involves the attachment of a 16-carbon palmitic acid to cysteine residues. Both modifications enhance the hydrophobicity of the protein, facilitating its association with cellular membranes. However, myristoylation is more conserved and often involved in signal transduction pathways, while palmitoylation is more dynamic and commonly associated with synaptic transmission. Understanding the attributes of these lipid modifications provides valuable insights into the complex regulatory mechanisms that govern protein behavior within cells.