OAS1 binds viral dsRNA

Human oligoadenylate synthetase 1 (OAS1) recognizes double-stranded RNA (dsRNA) typically produced by viral infections. The X-ray crystal structure of human OAS1 bound to a model 18-bp dsRNA duplex revealed that dsRNA binding allosterically drives a functionally essential structural reorganization within human OAS1 that narrows the adenosine triphosphate (ATP)-binding cleft and repositions a catalytic residue to complete its active site (Donovan J et al. 2013). Once stimulated by dsRNA, OAS1 uses ATP to synthesize a series of 5'-triphosphorylated 2'-5'-linked oligoadenylates containing 2 to greater than 5 adenylyl residues. The 5'-triphosphorylated 2'-5’-linked triadenylate (i.e., ppp5’A2’p5’A2’p5’A) is typically the most abundant active species (Kerr IM & Brown RE 1978).

人类寡腺苷酸合成酶1（OAS1）能够识别由病毒感染产生的双链RNA（dsRNA）。通过对结合于模型18碱基对双链RNA的二聚体的OAS1的人体X射线晶体结构进行分析，揭示了dsRNA的结合以别构方式驱动了人类OAS1中功能至关重要的结构重排，这一重排缩小了腺苷三磷酸（ATP）结合裂隙，并将一个催化基团重新定位以完善其活性位点（Donovan J et al. 2013）。一旦被dsRNA激活，OAS1便利用ATP合成一系列5'-三磷酸化2'-5'-连接的寡腺苷酸，这些寡腺苷酸含有2至大于5个腺苷基团。5'-三磷酸化2'-5’-连接的三腺苷酸（即，ppp5’A2’p5’A2’p5’A）通常是含量最丰富的活性物种（Kerr IM & Brown RE 1978）。