Mastering Myristoylation: The Key to Protein Function and Regulation

Myristoylation is a process by which a fatty acid called myristate is covalently attached to the N-terminal glycine residue of a protein. This modification is essential for the proper functioning of many cellular processes such as protein-protein interactions, protein localization, and signal transduction. In this article, we will discuss the significance of myristoylation and its role in various cellular activities.

One of the most well-known functions of myristoylation is in the regulation of G-protein signaling. G-proteins are involved in the transduction of extracellular signals to the inside of the cell, and the myristoylation of their N-terminus is essential for their proper localization and activation. For example, Gα subunits require adenylate cyclase, which catalyzes the production of cyclic AMP (cAMP), as a downstream effector. This process is facilitated by the binding of myristoylated Gα subunits to the plasma membrane, which is necessary for their interaction with downstream effectors.

Another significant function of myristoylation is in the regulation of protein-protein interactions. In particular, the myristoylation of the HIV-1 Nef protein has been shown to be critical in its function. Nef plays a critical role in the pathogenesis of HIV-1 by downregulating the expression of MHC-I on the surface of infected cells, which impairs the host immune response. Myristoylation of Nef is essential for its localization to the plasma membrane and interaction with specific host proteins.

Moreover, myristoylation is also crucial for the proper localization of some viral and bacterial proteins. For instance, the myristoylation of the RSV G protein is essential for its proper conformation and interaction with host cells. Similarly, the myristoylation of the Plasmodium falciparum acyl carrier protein is critical for its interaction with other enzymes in the fatty acid biosynthesis pathway within the parasite.

Finally, myristoylation has been implicated in the regulation of apoptosis. Cellular proteins are often modified during the different stages of apoptosis, and myristoylation has been found to play a role in mitochondrial apoptosis. Specifically, the myristoylation of the pro-apoptotic protein Smac/Diablo is essential for its localization in the mitochondrial intermembrane space, where it interacts with anti-apoptotic proteins such as XIAP, promoting apoptosis.

In conclusion, myristoylation is a critical post-translational modification that is essential for the proper functioning of many cellular processes. It plays a role in protein-protein interactions, signal transduction, and protein localization. Understanding the significance of myristoylation is essential for developing new therapies to treat a variety of diseases where this modification is implicated.