On Dec. 5, 2011, Proceedings of the National Academy of Sciences (PNAS) published online a paper entitled “Structural Insights into Protein Arginine Symmetric Dimethylation by PRMT5”, which is the fruit of a collaboration among the groups of  Ruiming Xu, Weimin Gong and Yingfang Liu at Institute of Biophysics and Shilai Bao’s group at Institute of Genetics and Developmental Biology.

Histone methylation occurs on both lysine and arginine residues. Lysine residues can be modified by addition of one, two or three methyl groups, while one or two methyl group may be added to an arginine. Symmetric and asymmetric dimethylation of arginine are isomeric protein posttranslational modifications with distinct biological effects, evidenced by the methylation of arginine 3 of histone H4 (H4R3): symmetric dimethylation of H4R3 leads to repression of gene expression, while asymmetric dimethylation of H4R3 is associated with gene activation.The enzymes catalyzing these modifications share identifiable sequence similarities, but the relationship between their catalytic mechanisms is unknown. We analyzed the structure of a prototypic symmetric arginine dimethylase, PRMT5, and discovered that a conserved phenylalanine in the active site is critical for specifying symmetric addition of methyl groups. Our results demonstrate a common catalytic mechanism intrinsic to both symmetric and asymmetric arginine dimethylases, and show that steric constrains in the active sites play an essential role in determining the product specificity of arginine methylases. This discovery also implies a potentially regulatable outcome of arginine dimethylation that may provide versatile control of eukaryotic gene expression.

This work was supported by grants from the Ministry of Science and Technology of China, the Natural Science Foundation of China and Chinese Academy of Sciences.

(http://www.pnas.org/content/early/2011/12/02/1106946108.abstract)