Type I Arginine Methyltransferases PRMT1 and PRMT-3 Act Distributively.
Asymmetric dimethylation of arginine residues is a common posttranslational modification of proteins carried out by type I protein arginine methyltransferases, including PRMT1 and -3. We report that the consecutive transfer of two methyl groups to a single arginine side chain by PRMT1 and -3 occurs in a distributive manner, i.e. with intermittent release of the monomethylated intermediate. The oligomeric state of PRMTs together with the clustering of methylated arginine residues in most proteins carrying this type of modification suggests that multiple methyl transfers to a single polypeptide chain might proceed in a processive manner by cooperation of multiple active sites. However, three different types of experiments provide evidence that the reaction is distributive even with substrates containing multiple methyl-accepting arginines, including one with 13 such residues. PRMT1 also does not prefer substrates already containing one or more singly or doubly methylated arginine residues. Even though the reaction is distributive, the efficiency of methylation of one particular protein strongly depends on the number of methyl-accepting arginine residues it contains.
Kölbel
Knut
K
Institute of Biochemistry and Biotechnology, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Str. 3.
Ihling
Christian
C
Bellmann-Sickert
Kathrin
K
Neundorf
Ines
I
Beck-Sickinger
Annette G
AG
Sinz
Andrea
A
Kühn
Uwe
U
Wahle
Elmar
E
D000818:Animals; D001120:Arginine / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008745:Methylation; D011499:Protein Processing, Post-Translational / Q000502:physiology; D011484:Protein-Arginine N-Methyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D011994:Recombinant Proteins; D012097:Repressor Proteins; D001120:Arginine; C099988:PRMT1 protein, human; C413164:PRMT3 protein, human; D011484:Protein-Arginine N-Methyltransferases