N-terminal protein myristoylation

Definition

Target type: biologicalprocess

The covalent attachment of a myristoyl group to the N-terminal amino acid residue of a protein. [GOC:mah]

N-terminal protein myristoylation is a type of lipid modification that plays a crucial role in cellular signaling and membrane association. It involves the covalent attachment of myristate, a 14-carbon saturated fatty acid, to the N-terminal glycine residue of a protein. The process is catalyzed by N-myristoyltransferase (NMT), a highly conserved enzyme present in all eukaryotic organisms.

Myristoylation typically occurs co-translationally, meaning it happens while the protein is being synthesized. The N-terminal glycine residue of the nascent polypeptide chain is exposed as the ribosome translocates the mRNA. NMT recognizes a specific amino acid sequence motif, often referred to as a "myristoylation signal," near the N-terminus of the protein. This motif typically consists of a glycine residue followed by a small hydrophobic amino acid, such as alanine, serine, or cysteine.

Once NMT binds to the target protein, it catalyzes the transfer of myristate from myristoyl-CoA, a coenzyme, to the N-terminal glycine residue. This reaction forms an amide bond between the carboxyl group of myristate and the amino group of glycine. The myristoylated protein is then released from NMT and can associate with cellular membranes.

Myristoylation is a highly specific and irreversible modification. It is essential for the proper function of a wide range of proteins, including:

* **Signal transduction proteins:** Myristoylation often targets proteins involved in signal transduction pathways, such as Src kinases and Ras GTPases. Myristate anchors these proteins to the plasma membrane, bringing them into close proximity with their signaling partners.
* **Membrane-associated proteins:** Many proteins that function at the cell membrane, such as G-protein coupled receptors and ion channels, are myristoylated. Myristoylation helps these proteins to associate with the lipid bilayer and perform their roles.
* **Viral proteins:** Some viral proteins, including the matrix protein of HIV-1, are myristoylated. This modification is essential for viral assembly and budding from host cells.

Myristoylation plays a critical role in regulating protein localization, activity, and interactions. It is a dynamic process that can be influenced by various cellular factors, including phosphorylation, ubiquitination, and other post-translational modifications. The study of N-terminal protein myristoylation continues to reveal important insights into the diverse functions of this lipid modification in cellular processes.'
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Proteins (3)

Compounds (7)