4ig8

Structural highlights

Function

OAS1_HUMAN Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes higher oligomers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication. Can mediate the antiviral effect via the classical RNase L-dependent pathway or an alternative antiviral pathway independent of RNase L. The secreted form displays antiviral effect against vesicular stomatitis virus (VSV), herpes simplex virus type 2 (HSV-2), and encephalomyocarditis virus (EMCV) and stimulates the alternative antiviral pathway independent of RNase L.^{[1] [2] [3] [4]}

References

1. ↑ Eskildsen S, Justesen J, Schierup MH, Hartmann R. Characterization of the 2'-5'-oligoadenylate synthetase ubiquitin-like family. Nucleic Acids Res. 2003 Jun 15;31(12):3166-73. PMID:12799444
2. ↑ Marques J, Anwar J, Eskildsen-Larsen S, Rebouillat D, Paludan SR, Sen G, Williams BR, Hartmann R. The p59 oligoadenylate synthetase-like protein possesses antiviral activity that requires the C-terminal ubiquitin-like domain. J Gen Virol. 2008 Nov;89(Pt 11):2767-72. doi: 10.1099/vir.0.2008/003558-0. PMID:18931074 doi:http://dx.doi.org/10.1099/vir.0.2008/003558-0
3. ↑ Lin RJ, Yu HP, Chang BL, Tang WC, Liao CL, Lin YL. Distinct antiviral roles for human 2',5'-oligoadenylate synthetase family members against dengue virus infection. J Immunol. 2009 Dec 15;183(12):8035-43. doi: 10.4049/jimmunol.0902728. Epub . PMID:19923450 doi:http://dx.doi.org/10.4049/jimmunol.0902728
4. ↑ Donovan J, Dufner M, Korennykh A. Structural basis for cytosolic double-stranded RNA surveillance by human oligoadenylate synthetase 1. Proc Natl Acad Sci U S A. 2013 Jan 14. PMID:23319625 doi:http://dx.doi.org/10.1073/pnas.1218528110