{"id":2819,"date":"2025-05-01T10:01:21","date_gmt":"2025-05-01T01:01:21","guid":{"rendered":"https:\/\/www.giar.gunma-u.ac.jp\/eng\/?p=2819"},"modified":"2025-05-01T13:40:41","modified_gmt":"2025-05-01T04:40:41","slug":"press-release20250501","status":"publish","type":"post","link":"https:\/\/www.giar.gunma-u.ac.jp\/eng\/press-release20250501\/","title":{"rendered":"\u3010Press Release\u3011Phase separation of the PRPP amidotransferase into dynamic condensates promotes de novo purine synthesis"},"content":{"rendered":"<p>An original research article &#8220;<a href=\"https:\/\/journals.plos.org\/plosbiology\/article?id=10.1371\/journal.pbio.3003111\">Phase separation of the PRPP amidotransferase into dynamic condensates promotes de novo purine synthesis in yeast<\/a>\u201d was published in PLOS Biology(IF 7.8).<\/p>\n<p>Purine nucleotides and their derivatives play crucial roles in many cellular processes, making them essential metabolites for all living organisms. Purine nucleotides are synthesized through salvage or de novo pathways. De novo purine synthesis (DPS) is up-regulated under conditions of high purine demand to ensure the production of genetic materials and chemical energy, thereby supporting cell proliferation. However, the regulatory mechanisms governing DPS remain unclear. We herein show that PRPP amidotransferase (PPAT), the rate-limiting enzyme in DPS, forms dynamic and motile condensates in cells under a purine-depleted environment. The formation and maintenance of condensates requires phase separation, which is driven by target of rapamycin complex 1-induced ribosome biosynthesis. The self-assembly of PPAT molecules facilitates condensate formation, with intracellular PRPP and purine nucleotides both regulating this self-assembly. Moreover, molecular dynamics simulations suggest that clustering-mediated PPAT activation occurs through intermolecular substrate channeling. Cells unable to form PPAT condensates exhibit growth defects, highlighting the physiological importance of condensation. Disorders in the regulation of purine metabolism are associated with various diseases, such as cancer and hyperuricemia (gout). Therefore, detailed examinations of DPS, including this study, will provide insights into the molecular mechanisms underlying these diseases.<br \/>\n<img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/www.giar.gunma-u.ac.jp\/eng\/wp-content\/uploads\/2025\/05\/20250501_eng.png\" alt=\"\" width=\"824\" height=\"345\" class=\"aligncenter size-full wp-image-3377\" \/><\/p>\n<p>\u25a0Title<br \/>\n<a href=\"https:\/\/journals.plos.org\/plosbiology\/article?id=10.1371\/journal.pbio.3003111\">Phase separation of the PRPP amidotransferase into dynamic condensates promotes de novo purine synthesis in yeast<\/a><\/p>\n<p style=\"font-size: 15.2px;\"><strong>Masak Takaine<\/strong><sup>1<\/sup><sup>*<\/sup>, Rikuri Morita<sup>2<\/sup>, Yuto Yoshinari<sup>3<\/sup> and Takashi Nishimura<sup>3<\/sup><br \/>\n1\u3000 GIAR, Gunma University, Maebashi, Japan, IMCR, Gunma University, Maebashi, Japan<br \/>\n2\u3000 Center for Computational Sciences, University of Tsukuba, Ibaraki, Japan<br \/>\n3\u3000 Laboratory of Metabolic Regulation and Genetics, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma, Japan<br \/>\n*, corresponding author<\/p>\n<p>\u25a0Journal<br \/>\n<a href=\"https:\/\/journals.plos.org\/plosbiology\/article?id=10.1371\/journal.pbio.3003111\">PLOS Biology<\/a>(IF 7.8)<\/p>\n<p>DOI\u756a\u53f7\u3000<a class=\"article-header__doi__value\" href=\"https:\/\/doi.org\/10.1371\/journal.pbio.3003111\">10.1371\/journal.pbio.3003111<\/a><\/p>\n<p>\u25a0Link<br \/>\n<a href=\"https:\/\/www.giar.gunma-u.ac.jp\/eng\/\">Gunma University Initiative for Advanced Research(GIAR)<\/a><br \/>\n<a href=\"https:\/\/www.imcr.gunma-u.ac.jp\/?lan=en\">Institute for Molecular and Cellular Regulation(IMCR)<\/a><br \/>\nGunma University <a href=\"https:\/\/www.gunma-u.ac.jp\/wp-content\/uploads\/2025\/05\/20250501-Press.pdf\">Press Release<\/a>(Original)<br \/>\n<a href=\"https:\/\/www.ccs.tsukuba.ac.jp\/eng\/\">Center for Computational Sciences, University of Tsukuba<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>An original research article &#8220;Phase separation of the PRPP amidotransferase into dynamic condensates pro [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[17],"tags":[],"class_list":["post-2819","post","type-post","status-publish","format-standard","hentry","category-research"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.giar.gunma-u.ac.jp\/eng\/wp-json\/wp\/v2\/posts\/2819","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.giar.gunma-u.ac.jp\/eng\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.giar.gunma-u.ac.jp\/eng\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.giar.gunma-u.ac.jp\/eng\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.giar.gunma-u.ac.jp\/eng\/wp-json\/wp\/v2\/comments?post=2819"}],"version-history":[{"count":6,"href":"https:\/\/www.giar.gunma-u.ac.jp\/eng\/wp-json\/wp\/v2\/posts\/2819\/revisions"}],"predecessor-version":[{"id":2828,"href":"https:\/\/www.giar.gunma-u.ac.jp\/eng\/wp-json\/wp\/v2\/posts\/2819\/revisions\/2828"}],"wp:attachment":[{"href":"https:\/\/www.giar.gunma-u.ac.jp\/eng\/wp-json\/wp\/v2\/media?parent=2819"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.giar.gunma-u.ac.jp\/eng\/wp-json\/wp\/v2\/categories?post=2819"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.giar.gunma-u.ac.jp\/eng\/wp-json\/wp\/v2\/tags?post=2819"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}