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Identification of a novel member of 2H phosphoesterases, 2ʹ,5ʹ-oligoadenylate degrading ribonuclease from the oyster Crassostrea gigas
Biochimie ( IF 3.9 ) Pub Date : 2018-09-05 , DOI: 10.1016/j.biochi.2018.09.003
Annika Lopp , Tõnu Reintamm , Anne Kuusksalu , Allan Olspert , Merike Kelve

Several genes of IFN-mediated pathways in vertebrates, among them the genes that participate in the 2ʹ,5ʹ-oligoadenylate synthetase (OAS)/RNase L pathway, have been identified in C. gigas. In the present study, we identified genes, which encode proteins having 2ʹ,5ʹ-oligoadenylate degrading activity in C. gigas. These proteins belong to the 2H phosphoesterase superfamily and have sequence similarity to the mammalian A kinase anchoring protein 7 (AKAP7) central domain, which is responsible for the 2ʹ,5ʹ-phosphodiesterase (2ʹ,5ʹ-PDE) activity. Comparison of the genomic structures of C. gigas proteins with that of AKAP7 suggests that these enzymes originate from a direct common ancestor. However, the identified nucleases are not typical 2ʹ,5ʹ-PDEs. The found enzymes catalyse the degradation of 2ʹ,5ʹ-linked oligoadenylates in a metal-ion-independent way, yielding products with 2ʹ,3ʹ -cyclic phosphate and 5ʹ-OH termini similarly to the 3ʹ−5ʹ bond cleavage in RNA, catalyzed by metal-independent ribonucleases. 3ʹ,5ʹ-linked oligoadenylates are not substrates for them. The preferred substrates for the C. gigas enzymes are 5ʹ-triphosphorylated 2ʹ,5ʹ-oligoadenylates, whose major cleavage reaction results in the removal of the 5ʹ-triphosphorylated 2ʹ,3ʹ-cyclic phosphate derivative, leaving behind the respective unphosphorylated 2ʹ,5ʹ-oligoadenylate. Such a cleavage reaction results in the direct inactivation of the biologically active 2–5A molecule. The 2ʹ,5ʹ-ribonucleases (2ʹ,5ʹ-RNases) from C. gigas could be members of the ancient group of ribonucleases, specific to 2ʹ−5ʹ phosphodiester bond, together with the enzyme that was characterized previously from the marine sponge Tethya aurantium. The novel 2ʹ,5ʹ-RNases may play a role in the control of cellular 2–5A levels, thereby limiting damage to host cells after viral infection.



中文翻译:

鉴定牡蛎Crassostrea gigas的2H磷酸酯酶的新成员2′,5′-寡腺苷酸降解核糖核酸酶

在脊椎动物IFN介导的途径的数个基因,其中的基因参与2',5'-寡腺苷酸合成酶(OAS)/ RNaseL途径,已中鉴定C.牡蛎。在本研究中,我们鉴定了基因,该基因编码在C. gigas中具有2′,5′-寡腺苷酸降解活性的蛋白质。这些蛋白质属于2H磷酸酯酶超家族,与哺乳动物A激酶锚定蛋白7(AKAP7)中央结构域具有序列相似性,后者负责2′,5′-磷酸二酯酶(2′,5′-PDE)的活性。C. gigas基因组结构的比较具有AKAP7的蛋白质表明这些酶起源于直接的共同祖先。但是,鉴定出的核酸酶不是典型的2′,5′-PDE。所发现的酶以不依赖金属离子的方式催化2ʹ,5ʹ连接的寡腺苷酸的降解,产生具有2ʹ,3ʹ环状磷酸酯和5ʹ-OH末端的产物,类似于在金属中催化的3ʹ-5ʹ键断裂。 -独立的核糖核酸酶。3ʹ,5ʹ连接的低聚腺苷酸不是它们的底物。C. gigas的首选底物酶是5′-三磷酸化的2′,5′-低聚腺苷酸,其主要裂解反应导致除去了5′-三磷酸化的2′,3′-环磷酸酯衍生物,留下了各自未磷酸化的2′,5′-低聚腺苷酸。这种裂解反应导致具有生物活性的2-5A分子直接失活。从2',5'-核糖核酸酶(2'-,5'-RNA酶)C.牡蛎可能是古组核糖核酸酶,具体的成员2'-5'-磷酸二酯键,与从海洋海绵先前表征的酶一起Tethya枳壳。新型的2′,5′-RNase可能在细胞2-5A水平控制中发挥作用,从而限制了病毒感染后对宿主细胞的损害。

更新日期:2018-09-05
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