CTP synthase forms cytoophidia in archaea

Shuang Zhou,Hua Xiang,Ji-Long Liu

doi:10.1016/j.jgg.2020.03.004

Abstract

CTP synthase (CTPS) is an important metabolic enzyme that catalyzes the rate-limiting reaction of nucleotide CTP de novo synthesis. Since 2010, a series of studies have demonstrated that CTPS can form filamentous structures in bacteria and eukaryotes, which are termed cytoophidia. However, it is unknown whether cytoophidia exist in the third domain of life, archaea. Using Haloarcula hispanica as a model system, here we demonstrate that CTPS forms distinct intracellular compartments in archaea. Under stimulated emission depletion microscopy, we find that the structures of H. hispanica CTPS are elongated, similar to cytoophidia in bacteria and eukaryotes. When Haloarcula cells are cultured in low-salt medium, the occurrence of cytoophidia increases dramatically. In addition, treatment of H. hispanica with a glutamine analog or overexpression of CTPS can promote cytoophidium assembly. Our study reveals that CTPS can form cytoophidia in all three domains of life, suggesting that forming cytoophidia is an ancient property of CTPS.

Highlights

CTP is the basic building block of RNA and DNA and the key precursor in the biosynthesis of membrane phospholipids (Carman and Henry, 1989)
We found that H. hispanica CTP synthase (HhCTPS) can form cytoophidia in E. coli (Figure 2d), but they are somewhat different to those formed by the E. coli CTP synthase (CTPS) (EcCTPS)
Our study demonstrates that CTPS forms cytoophidia in bacteria and eukaryotes and in archaea

Summary

Introduction

CTP (cytidine triphosphate) is the basic building block of RNA and DNA and the key precursor in the biosynthesis of membrane phospholipids (Carman and Henry, 1989). The synthesis of CTP is the last committed step in pyrimidine nucleotide de novo synthesis catalyzed by CTP synthase (CTPS) (Koshland Jr and Levitzki, 1974). This catalytic reaction includes the ATP-dependent phosphorylation at the C-4 position of UTP to form intermediate 4phosphoryl UTP, which is reacted with ammonia from glutamine hydrolysis to generate CTP (Lieberman, 1956; Long and Koshland, 1978). In 2010, CTPS was found to compartmentalize into filamentous structures in Drosophila These structures are termed cytoophidia (cellular snakes in Greek) (Liu, 2010). The phenomenon that CTPS forms cytoophidia is conserved across bacteria and eukaryotes

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