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How the activity of PRMT1 is regulated is therefore paramount, but is not clearly understood. Several studies have observed higher order oligomeric species of PRMT1, but it is unclear if these exist at physiological concentrations and there is confusion in the literature about how oligomerization affects activity. We therefore sought to determine which oligomeric species of PRMT1 are physiologically relevant, and quantitatively correlate activity with specific oligomer forms. Through quantitative western blotting, we determined that concentrations of PRMT1 available in a variety of human cell lines are in the sub\u2010micromolar to low micromolar range. Isothermal spectral shift binding data were modeled to a monomer\/dimer\/tetramer equilibrium with an EC\n                    <jats:sub>50<\/jats:sub>\n                    for tetramer dissociation of ~20\u2009nM. A combination of sedimentation velocity and Native polyacrylamide gel electrophoresis experiments directly confirmed that the major oligomeric species of PRMT1 at physiological concentrations would be dimers and tetramers. Surprisingly, the methyltransferase activity of a dimeric PRMT1 variant is similar to wild type, tetrameric PRMT1 with some purified substrates, but dimer and tetramer forms of PRMT1 show differences in catalytic efficiencies and substrate specificity for other substrates. Our results define an oligomerization paradigm for PRMT1, show that the biophysical characteristics of PRMT1 are poised to support a monomer\/dimer\/tetramer equilibrium in vivo, and suggest that the oligomeric state of PRMT1 could be used to regulate substrate specificity.\n                  <\/jats:p>","DOI":"10.1002\/pro.5118","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T05:43:05Z","timestamp":1721281385000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Oligomerization of protein arginine methyltransferase 1 and its effect on methyltransferase activity and substrate specificity"],"prefix":"10.1002","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3157-9077","authenticated-orcid":false,"given":"Vincent","family":"Rossi","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry Utah State University  Logan Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8070-4350","authenticated-orcid":false,"given":"Sarah E.","family":"Nielson","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Utah State University  Logan Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariana","family":"Ortolano","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Utah State University  Logan Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6751-8018","authenticated-orcid":false,"given":"Isabella","family":"Lonardo","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Utah State University  Logan Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6785-4859","authenticated-orcid":false,"given":"Emeline","family":"Haroldsen","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Utah State University  Logan Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drake","family":"Comer","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Utah State University  Logan Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5894-9022","authenticated-orcid":false,"given":"Owen M","family":"Price","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Utah State University  Logan Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Wallace","sequence":"additional","affiliation":[{"name":"NanoTemper Technologies  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9559-4635","authenticated-orcid":false,"given":"Joan M.","family":"Hevel","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry Utah State University  Logan Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2019.02.072"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389203721666200507091952"},{"key":"e_1_2_9_4_1","unstructured":"Anon cancer.sanger.ac.uk\/cosmic."},{"key":"e_1_2_9_5_1","unstructured":"Anon Human Protein Atlas. 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