peptidyl-arginine N-methylation

Definition

Target type: biologicalprocess

The addition of a methyl group onto a nitrogen atom of an arginine residue in a protein. [GOC:bf]

Peptidyl-arginine N-methylation is a post-translational modification (PTM) that plays a crucial role in regulating protein function and cellular processes. This modification involves the addition of a methyl group to the guanidino nitrogen of an arginine residue within a protein. The process is catalyzed by a family of enzymes called protein arginine methyltransferases (PRMTs). There are 11 known PRMTs in mammals, each with distinct substrate specificities and cellular functions.

The methylation reaction occurs in two steps:

1. **Formation of a SAM-enzyme complex:** S-adenosyl methionine (SAM), a universal methyl donor in biological systems, binds to the active site of the PRMT. This binding event creates a complex that positions SAM for the methylation reaction.

2. **Methyl transfer:** The guanidino nitrogen of the arginine residue within the target protein interacts with the active site of the PRMT. This interaction facilitates the transfer of the methyl group from SAM to the arginine residue, forming monomethylarginine (MMA). The enzyme then releases the product, monomethylated protein, and the demethylated SAM molecule, S-adenosyl homocysteine (SAH).

The methylation of arginine residues can occur in different positions within the guanidino group, leading to the formation of monomethylarginine (MMA), asymmetric dimethylarginine (ADMA), or symmetric dimethylarginine (SDMA). The specific type of methylation product depends on the PRMT involved. For example, PRMT1 and PRMT4 mainly produce ADMA, while PRMT5 produces symmetrically dimethylated arginine (SDMA).

Peptidyl-arginine N-methylation has been implicated in a wide range of cellular processes, including:

* **Gene regulation:** Methylation of arginine residues within histones can alter chromatin structure and regulate gene expression.
* **Signal transduction:** Methylation of proteins involved in signaling pathways can modulate their activity and influence cellular responses.
* **Protein-protein interactions:** Methylation of arginine residues can create binding sites for other proteins, facilitating protein-protein interactions.
* **RNA processing:** Methylation of RNA-binding proteins can regulate RNA splicing, translation, and stability.
* **Cellular stress response:** Methylation of stress-responsive proteins can modulate their activity and contribute to the cellular response to stress.

The dysregulation of peptidyl-arginine N-methylation has been linked to several diseases, including cancer, neurodegenerative disorders, and cardiovascular disease. For example, dysregulated PRMT activity has been associated with increased tumor growth and metastasis. Understanding the biological role of peptidyl-arginine N-methylation is crucial for developing new therapeutic strategies for these diseases.'
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Proteins (1)

Compounds (12)