5w5i

Structural highlights

Function

[IFIT1_HUMAN] Interferon-induced antiviral RNA-binding protein that specifically binds single-stranded RNA bearing a 5'-triphosphate group (PPP-RNA), thereby acting as a sensor of viral single-stranded RNAs and inhibiting expression of viral messenger RNAs. Single-stranded PPP-RNAs, which lack 2'-O-methylation of the 5' cap and bear a 5'-triphosphate group instead, are specific from viruses, providing a molecular signature to distinguish between self and non-self mRNAs by the host during viral infection. Directly binds PPP-RNA in a non-sequence-specific manner. Viruses evolved several ways to evade this restriction system such as encoding their own 2'-O-methylase for their mRNAs or by stealing host cap containing the 2'-O-methylation (cap snatching mechanism). Exhibits antiviral activity against several viruses including human papilloma and hepatitis C viruses.^{[1] [2] [3] [4]}

References

1. ↑ Terenzi F, Saikia P, Sen GC. Interferon-inducible protein, P56, inhibits HPV DNA replication by binding to the viral protein E1. EMBO J. 2008 Dec 17;27(24):3311-21. doi: 10.1038/emboj.2008.241. Epub 2008 Nov, 13. PMID:19008854 doi:http://dx.doi.org/10.1038/emboj.2008.241
2. ↑ Li Y, Li C, Xue P, Zhong B, Mao AP, Ran Y, Chen H, Wang YY, Yang F, Shu HB. ISG56 is a negative-feedback regulator of virus-triggered signaling and cellular antiviral response. Proc Natl Acad Sci U S A. 2009 May 12;106(19):7945-50. doi:, 10.1073/pnas.0900818106. Epub 2009 Apr 28. PMID:19416887 doi:http://dx.doi.org/10.1073/pnas.0900818106
3. ↑ Raychoudhuri A, Shrivastava S, Steele R, Kim H, Ray R, Ray RB. ISG56 and IFITM1 proteins inhibit hepatitis C virus replication. J Virol. 2011 Dec;85(24):12881-9. doi: 10.1128/JVI.05633-11. Epub 2011 Oct 5. PMID:21976647 doi:http://dx.doi.org/10.1128/JVI.05633-11
4. ↑ Abbas YM, Pichlmair A, Gorna MW, Superti-Furga G, Nagar B. Structural basis for viral 5'-PPP-RNA recognition by human IFIT proteins. Nature. 2013 Jan 13. doi: 10.1038/nature11783. PMID:23334420 doi:http://dx.doi.org/10.1038/nature11783