CTP synthase forms cytoophidia in archaea

CTP synthase (CTPS) is an important metabolic enzyme that catalyzes the rate-limiting reaction of de novo synthesis of the nucleotide CTP. Since 2010, a series studies have demonstrated that CTPS can form filamentous structures termed cytoophidia in bacteria and eukaryotes. However, it remains unknown whether cytoophidia exist in archaea, the third domain of life. Using Haloarcula hispanica as a model system, here we demonstrate that CTPS forms distinct intracellular compartments in archaeal cells. Under stimulated emission depletion (STED) microscopy, we find that those HhCTPS compartments are elongated filamentous structure, resembling cytoophidia in bacteria and eukaryotes. When Haloarcula cells cultured in low-salt medium, the occurrence of cytoophidia increases dramatically. Moreover, overexpression CTPS or glutamine analog treatment promote cytoophidium assembly in H. hispanica. Our study reveals that CTPS forms cytoophidia in all three domains of life, suggesting that forming cytoophidia is an ancient property of CTPS. Summary Author CTP synthase (CTPS), as a textbook molecule, has been studied biochemically for almost 70 years. It catalyses the last step of making up the nucleotide CTP. Since biochemical properties and the regulatory mechanisms of CTPS were thoroughly studied in the past decades, it came as a surprise when a new feature of CTPS was revealed in 2010. Multiple studies reveal that CTPS can form snakeshaped structures termed cytoophidia in bacteria and eukaryotes. However, it is not clear whether cytoophidia exist in archaea, the third domain of life. Here we use halophilic archaeon Haloarcula hispanica as a model and show that CTPS can form defined structures in archaea. Using super resolution microscopy, we confirm that those CTPS-containing structures are elongated filaments, similar to cytoophidia described in bacteria and eukaryotic cells. Therefore, this study demonstrates that CTPS forms cytoophidia not only in bacteria and eukaryotes, but also in archaea.