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-Structure paper
タイトル | Two RNA-binding motifs in eIF3 direct HCV IRES-dependent translation. |
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ジャーナル・号・ページ | Nucleic Acids Res, Vol. 41, Issue 15, Page 7512-7521, Year 2013 |
掲載日 | 2013年6月13日 |
著者 | Chaomin Sun / Jordi Querol-Audí / Stefanie A Mortimer / Ernesto Arias-Palomo / Jennifer A Doudna / Eva Nogales / Jamie H D Cate / |
PubMed 要旨 | The initiation of protein synthesis plays an essential regulatory role in human biology. At the center of the initiation pathway, the 13-subunit eukaryotic translation initiation factor 3 (eIF3) ...The initiation of protein synthesis plays an essential regulatory role in human biology. At the center of the initiation pathway, the 13-subunit eukaryotic translation initiation factor 3 (eIF3) controls access of other initiation factors and mRNA to the ribosome by unknown mechanisms. Using electron microscopy (EM), bioinformatics and biochemical experiments, we identify two highly conserved RNA-binding motifs in eIF3 that direct translation initiation from the hepatitis C virus internal ribosome entry site (HCV IRES) RNA. Mutations in the RNA-binding motif of subunit eIF3a weaken eIF3 binding to the HCV IRES and the 40S ribosomal subunit, thereby suppressing eIF2-dependent recognition of the start codon. Mutations in the eIF3c RNA-binding motif also reduce 40S ribosomal subunit binding to eIF3, and inhibit eIF5B-dependent steps downstream of start codon recognition. These results provide the first connection between the structure of the central translation initiation factor eIF3 and recognition of the HCV genomic RNA start codon, molecular interactions that likely extend to the human transcriptome. |
リンク | Nucleic Acids Res / PubMed:23766293 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 20.0 Å |
構造データ | EMDB-2198: EMDB-2199: |
由来 |
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