Human protein arginine methyltransferases (PRMTs) can be optimally active under nonphysiological conditions
| Autor: | Troy L, Lowe, Steven G, Clarke |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Protein-Arginine N-Methyltransferases
Biochemistry & Molecular Biology intracellular stress Arginine Biochemistry Methylation Medical and Health Sciences Humans histone methylation protein methylation temperature dependence Molecular Biology Protein Processing posttranslational modification S-adenosylmethionine Osmolar Concentration protein arginine N-methyltransferase 5 Temperature Post-Translational Cell Biology Hydrogen-Ion Concentration Biological Sciences pH effects Chemical Sciences Protein Processing Post-Translational ionic strength |
| Zdroj: | The Journal of biological chemistry, vol 298, iss 9 |
| Popis: | Protein arginine methylation is involved in many biological processes and can be enhanced in cancer. In mammals, these reactions are catalyzed on multiple substrates by a family of nine protein arginine methyltransferases (PRMTs). However, conditions that may regulate the activity of each enzyme and that may help us understand the physiological role of PRMTs have not been fully established. Previous studies had suggested unexpected effects of temperature and ionic strength on PRMT7 activity. Here we examine in detail the effects of temperature, pH, and ionic strength on recombinant human PRMT1, PRMT5, and PRMT7. We confirmed the unusual temperature dependence of PRMT7, where optimal activity was observed at 15 °C. On the other hand, we found that PRMT1 and PRMT5 are most active near physiological temperatures of 37 °C. However, we showed all three enzymes still have significant activity at 0 °C. Furthermore, we determined that PRMT1 is most active at a pH of about 7.7, while PRMT5 activity is not dependent on pH in the range of 6.5 to 8.5. Significantly, PRMT7 is most active at an alkaline pH of 8.5 but shows little activity at the physiological intracellular pH of about 7.2. We also detected decreased activity at physiological salt conditions for PRMT1, PRMT5, and PRMT7. We demonstrate that the loss of activity is due to the increasing ionic strength. Taken together, these results open the possibility that PRMTs respond in cells undergoing temperature, salt, or pH stress and demonstrate the potential for invivo regulation of protein arginine methylation. |
| Databáze: | OpenAIRE |
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