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Arginine peptide methylation in cell signalling.

 
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10/13/2013

Arginine peptide methylation in cell signalling.

Arginine peptide methylation in cell signalling
 
The posttranslational methylation of arginines is commonly found in a variety of proteins present in a cell and maybe an important part of cell signalling. The modification results in the mono- and dimethylation of the guanidine nitrogen atoms of arginine. The dimethylation of arginines can occur in a symmetrical or asymmetrical manner resulting in symmetrical dimethylated arginine (sDMA) and asymmetrical dimethylated arginine (aDMA). All three possible methylated arginines have been found in eukaryotes. The methylation of arginine residues is catalyzed by protein arginine methyltransferases (PRMT) which are classified according to the mode of methylation. The methylation of arginine residues creates binding sites for recognition of methylarginine-binding domains, or sterically hinders other proteins from binding to neighboring post-translational modified sites. It is now known that the methylation of arginine residues in cellular proteins plays an important role in cell signaling and cellular regulation where it is involved in the modulation of protein-protein interphases. One example is the interaction of Tudor domains with methylated PIWI proteins which is thought to regulate the PIWI-interacting RNA pathway in the germ line. Furthermore, three out of seven proteins that make up the Sm core possess symmetric dimethylarginine (sDMA). The Sm core is essential for the biogenesis, transport and function of small nuclear ribonucleic acid binding protein (snRNP) particles. Sm proteins were named in honor of Stephanie Smith, a patient who suffered from systemic lupus erythematosus SLE were so-called Anti-Sm antibodies were discovered. Originally it was thought that arginine methylation is irreversible. However, this changed when it was discovered that methylated arginine can be converted into citrulline by enzymes. Even though the exact roles of this type of modifications is still not very well understood presently it is thought that they play important roles in cell signaling pathways that involve RNA processing, such as packaging and exporting from the nucleus into the cytosol, transcription regulation, signal transduction and DNA repair. Improvements made in automated solid-phase-peptide synthesis have recently enabled efficient routine synthesis of peptides containing methylated arginine residues. Fmoc protected methylated arginine monomers are now available to allow for the efficient automated synthesis of mono- and dimethylated-arginine rich peptides.

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