The Role of 2', 5'-Oligoadenylate Synthetase Gene in Interferon System

2'， 5'-寡腺苷合成酶（OAS），干扰素（IFN）诱导酶，由双链RNA激活，合成2'， 5'-寡腺苷（2-5A）使用ATP作为一种底物。以下的结果是由这项赠款资助的研究获得的。（1）一个P-环路由含有Asp-contained sequence （参考为D-box）和含有大量Lys和Arg （KR-富地区）的区域由各种OAS子类型组成。The experiments of the site-directed mutations into these motifs demonstrated that these motifs are important for the enzymatic activities of OAS ：Mgy D12+イエD1 binds to the D-box and ATP may interact to both P-loop and KR-rich region。（2）ChOAS的基因由6个exons和5个intron组成，其中第6个exons编码了类似于泛素（UBL）的域和第1个到第5个exons编码了催化域。ChOAS基因在最少两个阵列中找到， OAS基因D1* Eye D1 A和OAS Eye D1* Eye D1 B，以及OAS Eye D1 B阵列只在各种鸡行中找到Leghorn。OAS-B在UBL域中有一种32-氨基酸的变体。（3）当OAS-A和OAS-B之间与OAS-B之间的酶质性质比较时，在低温下进行热处理和去除的情况更加明显。Furthermore， OAS-B对蛋白质治疗和消化更有敏感性。这些结果表明了UBL域的稳定性，该结构的催化域的构成。（4）在对上述结果的补充中，根据美洲国家组织的定义确定了IFN行动的目标站点。

2', 5'-Olioadenylate synthetase (OAS), an interferon (IFN)-induced enzyme, is activated by double-stranded RNA and synthesizes 2', 5'-oligoadenylate (2-5A) using ATP as a substrate. The following results were obtained from the research aided by this grant.(1) A P-loop motif followed by an Asp-containing sequence (referred to as D-box) and a region with a high content of Lys and Arg (KR-rich region) are conserved in various OAS subtypes. The experiments of the site-directed mutations into these motifs demonstrated that these motifs are important for the enzymatic activities of OAS : MgィイD12+ィエD1 binds to the D-box and ATP may interact to both P-loop and KR-rich region.(2) The gene for ChOAS is composed of 6 exons and 5 introns, in which the 6th exon encodes an ubiquitin-like (UbL) domain and the 1st to 5th exons encode the catalytic domain. The ChOAS gene has at least two alleles, OASィイD1*ィエD1A and OASィイD1*ィエD1B, and OASィイD1*ィエD1B allele was found only in Leghorn among various chicken lines. OAS-B has a deletion of 32-amino acids in the UbL domain.(3) When compared the enzymatic nature between OAS-A and B, OAS-B was more labile to heat-treatment and denatured at low temperature. Furthermore, OAS-B was more sensitive to protease-treatment and digested easily. These results indicate that the UbL domain stabilizes the conformation of the catalytic domain of this enzyme.(4) In addition to the above results, the target sites of IFN action in tissues were determined by the induction of OAS.