Class
Article
College
College of Science
Faculty Mentor
Joan Hevel
Presentation Type
Poster Presentation
Abstract
Protein arginine methyl transferases (PRMTs) are a family of proteins that modify protein targets though the addition of a methyl group. PRMTs play roles in DNA repair, cancer, heart disease, epigenetic programming, and many other cellular functions. The biochemical mechanisms that govern PRMT regulation are still poorly understood. Additionally, arginine methylation appears to be a permanent modification, as no arginine demethylases have been identified. This implicates a further importance of proper PRMT regulation. The Hevel lab has recently characterized an intrinsic redox dependent modulator of PRMT1 activity. We showed that cysteines 101 and 208 of PRMT1 sense redox conditions, which gives rise to altered enzymatic activity. Interestingly, we have also observed redox sensitivity in PRMT6, a protein highly homologous to PRMT1. Comparisons of oxidized and reduced PRMT6 crystal structures show that cysteine residues non-homologous to those identified in PRMT1 form a disulfide bond, a different type of oxidized cysteine. This implies that the mechanism of redox regulation in PRMT6 may be different than in PRMT1. We hypothesize that one or several of these cysteine residues are responsible for the redox induced modulation of PRMT6 activity. To test this hypothesis, we will assay mutant cysteineless PRMT6 protein for activity in both oxidative and reductive conditions. These results will then be compared to wild type PRMT6 assayed under the same redox conditions. Major differences in the activity of the enzymes will confirm that cysteines play a regulatory role in PRMT6 activity.
Location
The South Atrium
Start Date
4-12-2018 10:30 AM
End Date
4-12-2018 11:45 AM
Is Redox Regulation of Protein Arginine Methyltransferase 6 Cysteine Mediated?
The South Atrium
Protein arginine methyl transferases (PRMTs) are a family of proteins that modify protein targets though the addition of a methyl group. PRMTs play roles in DNA repair, cancer, heart disease, epigenetic programming, and many other cellular functions. The biochemical mechanisms that govern PRMT regulation are still poorly understood. Additionally, arginine methylation appears to be a permanent modification, as no arginine demethylases have been identified. This implicates a further importance of proper PRMT regulation. The Hevel lab has recently characterized an intrinsic redox dependent modulator of PRMT1 activity. We showed that cysteines 101 and 208 of PRMT1 sense redox conditions, which gives rise to altered enzymatic activity. Interestingly, we have also observed redox sensitivity in PRMT6, a protein highly homologous to PRMT1. Comparisons of oxidized and reduced PRMT6 crystal structures show that cysteine residues non-homologous to those identified in PRMT1 form a disulfide bond, a different type of oxidized cysteine. This implies that the mechanism of redox regulation in PRMT6 may be different than in PRMT1. We hypothesize that one or several of these cysteine residues are responsible for the redox induced modulation of PRMT6 activity. To test this hypothesis, we will assay mutant cysteineless PRMT6 protein for activity in both oxidative and reductive conditions. These results will then be compared to wild type PRMT6 assayed under the same redox conditions. Major differences in the activity of the enzymes will confirm that cysteines play a regulatory role in PRMT6 activity.