Regulation of Protein Arginine Methyltransferase 8 (PRMT8) Activity by Its N-terminal Domain
| Autor: | Donghang Cheng, Joyce Sayegh, Steven Clarke, Mark T. Bedford, Kristofor J. Webb |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Protein-Arginine N-Methyltransferases
Recombinant Fusion Proteins Proteolysis Biology Methylation Biochemistry law.invention src Homology Domains law medicine Humans Binding site Molecular Biology Peptide sequence Myristoylation Protein arginine methyltransferase 8 chemistry.chemical_classification Binding Sites Sequence Homology Amino Acid medicine.diagnostic_test Membrane Proteins Cell Biology Fusion protein Enzyme Activation Repressor Proteins Enzyme chemistry Recombinant DNA Protein Processing Post-Translational HeLa Cells |
| Zdroj: | Journal of Biological Chemistry. 282:36444-36453 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m704650200 |
| Popis: | Human protein arginine methyltransferase PRMT8 has been recently described as a type I enzyme in brain that is localized to the plasma membrane by N-terminal myristoylation. The amino acid sequence of human PRMT8 is almost 80% identical to human PRMT1, the major protein arginine methyltransferase activity in mammalian cells. However, the activity of a recombinant PRMT8 GST fusion protein toward methyl-accepting substrates is much lower than that of a GST fusion of PRMT1. We show here that both His-tagged and GST fusion species lacking the initial 60 amino acid residues of PRMT8 have enhanced enzymatic activity, suggesting that the N-terminal domain may regulate PRMT8 activity. This conclusion is supported by limited proteolysis experiments showing an increase in the activity of the digested full-length protein, consistent with the loss of the N-terminal domain. In contrast, the activity of the N-terminal truncated protein was slightly diminished by limited proteolysis. Significantly, we detect automethylation at two sites in the N-terminal domain, as well as binding sites for SH3 domain-containing proteins. We suggest that the N-terminal domain may function as an autoregulator that may be displaced by interaction with one or more physiological inducers. |
| Databáze: | OpenAIRE |
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