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Human IFIT3 Modulates IFIT1 RNA Binding Specificity and Protein Stability.
- Source :
-
Immunity (10747613) . Mar2018, Vol. 48 Issue 3, p487-499.e5. 1p. - Publication Year :
- 2018
-
Abstract
- Summary Although interferon-induced proteins with tetratricopeptide repeats (IFIT proteins) inhibit infection of many viruses by recognizing their RNA, the regulatory mechanisms involved remain unclear. Here we report a crystal structure of cap 0 (m 7 GpppN) RNA bound to human IFIT1 in complex with the C-terminal domain of human IFIT3. Structural, biochemical, and genetic studies suggest that IFIT3 binding to IFIT1 has dual regulatory functions: (1) extending the half-life of IFIT1 and thereby increasing its steady-state amounts in cells; and (2) allosterically regulating the IFIT1 RNA-binding channel, thereby enhancing the specificity of recognition for cap 0 but not cap 1 (m 7 GpppNm) or 5′-ppp RNA. Mouse Ifit3 lacks this key C-terminal domain and does not bind mouse Ifit1. The IFIT3 interaction with IFIT1 is important for restricting infection of viruses lacking 2′-O methylation in their RNA cap structures. Our experiments establish differences in the regulation of IFIT1 orthologs and define targets for modulation of human IFIT protein activity. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10747613
- Volume :
- 48
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Immunity (10747613)
- Publication Type :
- Academic Journal
- Accession number :
- 128514815
- Full Text :
- https://doi.org/10.1016/j.immuni.2018.01.014