6C6K
Structural basis for preferential recognition of cap 0 RNA by a human IFIT1-IFIT3 protein complex
Summary for 6C6K
| Entry DOI | 10.2210/pdb6c6k/pdb |
| Descriptor | Interferon-induced protein with tetratricopeptide repeats 1, Interferon-induced protein with tetratricopeptide repeats 3, RNA (5'-R((M7G)*P*AP*UP*AP*GP*GP*CP*GP*GP*CP*G)-3'), ... (5 entities in total) |
| Functional Keywords | innate immunity, interferon stimulated genes, host defense, antiviral, self/non-self rna recognition, pathogen associated molecular patterns, flavivirus, rna binding protein-rna complex, rna binding protein/rna |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 125662.93 |
| Authors | Amarasinghe, G.K.,Leung, D.W.,Johnson, B.,Xu, W. (deposition date: 2018-01-18, release date: 2018-04-04, Last modification date: 2024-03-06) |
| Primary citation | Johnson, B.,VanBlargan, L.A.,Xu, W.,White, J.P.,Shan, C.,Shi, P.Y.,Zhang, R.,Adhikari, J.,Gross, M.L.,Leung, D.W.,Diamond, M.S.,Amarasinghe, G.K. Human IFIT3 Modulates IFIT1 RNA Binding Specificity and Protein Stability. Immunity, 48:487-499.e5, 2018 Cited by PubMed Abstract: 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 (mGpppN) 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 (mGpppNm) 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. PubMed: 29525521DOI: 10.1016/j.immuni.2018.01.014 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.54 Å) |
Structure validation
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