Myristoylation

Myristoylation is a lipid modification process in which a myristoyl group, derived from myristic acid, is covalently attached to the amino-terminal glycine residue of a protein molecule. This post-translational modification is crucial for the proper function and localization of proteins within the cell. Myristoylation enables proteins to associate with cell membranes, which is essential for signal transduction, protein-protein interactions, and membrane trafficking.

Mechanism

Myristoylation typically occurs co-translationally, meaning it happens during the synthesis of the protein on ribosomes. The enzyme N-myristoyltransferase (NMT) catalyzes the transfer of the myristoyl group from myristoyl-CoA to the N-terminal glycine residue of the nascent protein. This process is irreversible, making the myristoylation of proteins a critical regulatory step in cellular function.

Function

The primary function of myristoylation is to anchor proteins to cellular membranes. This lipid modification increases the hydrophobicity of the protein, facilitating its association with the lipid bilayer. Myristoylated proteins play vital roles in various cellular processes, including:

• Signal transduction: Many signaling proteins require myristoylation for membrane localization and function. For example, Src family kinases, which are involved in regulating cell growth and differentiation, are myristoylated.
• Protein-protein interactions: Myristoylation can influence the interaction between proteins, affecting the assembly of protein complexes necessary for cellular signaling and function.
• Membrane trafficking: Proteins involved in the trafficking of vesicles within the cell, such as members of the ADP-ribosylation factor family, are often myristoylated to ensure proper localization and function.

Clinical Significance

Alterations in myristoylation can lead to various diseases, including cancer, viral infections, and neurodegenerative disorders. For instance, the overexpression of N-myristoyltransferase has been observed in certain types of cancer, suggesting a role in tumorigenesis. Additionally, some viruses hijack the host's myristoylation machinery to ensure the proper assembly and function of viral proteins, making NMT a potential target for antiviral therapy.

Research and Therapeutic Approaches

Given its importance in numerous cellular processes and disease states, myristoylation has become a target for therapeutic intervention. Inhibitors of N-myristoyltransferase are being explored as potential treatments for cancer and viral infections. Furthermore, understanding the specific roles of myristoylation in neurodegenerative diseases may lead to novel therapeutic strategies for these conditions.

See Also

• Lipidation
• Post-translational modification
• Protein targeting
• Signal transduction