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Cellular response to viral infection is mediated by the viral stress-inducible genes which
can be independently induced by interferons, double-stranded RNA, and many viruses.
Two well-studied interferon-induced viral stress-inducible genes are for the 2’-5’-oligoadenylate
synthetases (OAS) and RNase L. OAS are double-stranded RNA-activated enzymes which oligomerize ATP
into 2’-5’-linked oligoadenylates, which in turn dimerize and active RNase L, an endoribonuclease.
We have recently determined the first crystal structure of an OAS family member. Our structure of the small
(single-module) OAS1 isozyme revealed a multi-domain protein fold and catalytic machinery similar to
those seen in polymerases, and led to complementary structure-based mutagenesis studies.
The protein fold contains two large domains connected by a short linker and tethered by contacts between the amino-
and carboxy- termini. The OAS1 crystal structure represents the latent form and comparison with polymerase
structures suggests a mechanism for double-stranded RNA activation that includes a domain-domain conformational shift.
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