EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural insights into the role of eIF3 in translation mediated by the HCV IRES.
ジャーナル・号・ページ	Proc Natl Acad Sci U S A, Vol. 122, Issue 49, Page e2505538122, Year 2025
掲載日	2025年12月9日
著者	Wakana Iwasaki / Kazuhiro Kashiwagi / Ayako Sakamoto / Madoka Nishimoto / Mari Takahashi / Kodai Machida / Hiroaki Imataka / Akinobu Matsumoto / Yuichi Shichino / Shintaro Iwasaki / Koshi Imami / Takuhiro Ito /
PubMed 要旨	The genomes of various RNA viruses and a subset of human genes contain structured RNA elements termed internal ribosomal entry sites (IRESs) to initiate translation in a cap-independent manner. The ...The genomes of various RNA viruses and a subset of human genes contain structured RNA elements termed internal ribosomal entry sites (IRESs) to initiate translation in a cap-independent manner. The well-studied IRES from Hepatitis C virus (HCV) binds to eukaryotic initiation factor 3 (eIF3), but how the HCV IRES harnesses eIF3 for viral translation remains unclear. Here, we determined multiple cryo-EM structures in which the HCV IRES binds simultaneously to the ribosome and eIF3, covering steps from initiation to elongation. The eIF3 core subunits are displaced from the ribosome by binding more tightly to subdomain IIIb of the HCV IRES. However, cross-linking mass spectrometry suggested that the eIF3 noncore subunits in the HCV-IRES-mediated elongation complex remain in similar positions on the ribosome to those observed in the cap-mediated initiation complex. This currently determined configuration of eIF3 core and noncore subunits reveals the mechanisms through which the HCV IRES overcomes the competition with the host mRNA and promotes viral mRNA translation by utilizing eIF3. Interestingly, cryo-EM structures also revealed that the N-terminal domain of the eIF3 c-subunit (eIF3c-NTD) binds to the large ribosomal subunit (60S) during elongation. These findings suggest that eIF3 contributes to HCV IRES-mediated translation not only during initiation but also elongation and potentially in reinitiation. The interaction between the eIF3c-NTD and the 60S ribosome is likely to occur in general translation processes as well, contributing to 60S joining or eIF3 stabilization on the elongating ribosome.
リンク	Proc Natl Acad Sci U S A / PubMed:41337487 / PubMed Central
手法	EM (単粒子)
解像度	3.0 - 3.3 Å
構造データ	62386 9kkf EMDB-62386, PDB-9kkf: Structure of the human 40S ribosome complexed with HCV IRES and eIF3 手法: EM (単粒子) / 解像度: 3.3 Å 62453 9kn5 EMDB-62453, PDB-9kn5: Structure of the human 40S ribosome complexed with HCV IRES, eIF1A and eIF3 手法: EM (単粒子) / 解像度: 3.2 Å 62454 9kn6 EMDB-62454, PDB-9kn6: Structure of the HCV IRES-dependent pre-48S translation initiation complex with eIF1A, eIF5B, and eIF3 手法: EM (単粒子) / 解像度: 3.3 Å 62535 9krp EMDB-62535, PDB-9krp: Structure of the HCV IRES-dependent 48S translation initiation complex with eIF5B and eIF3 手法: EM (単粒子) / 解像度: 3.2 Å 62671 9kzu EMDB-62671, PDB-9kzu: Cryo-EM structure of the HCV IRES-dependently initiated CMV-stalled 80S ribosome (non-rotated state) in complexed with eIF3 手法: EM (単粒子) / 解像度: 3.0 Å 62679 9kzx EMDB-62679, PDB-9kzx: Cryo-EM structure of the HCV IRES-dependently initiated CMV-stalled 80S ribosome (rotated state) in complexed with eIF3 手法: EM (単粒子) / 解像度: 3.3 Å
化合物	ChemComp-ZN: Unknown entry ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-GTP: GUANOSINE-5'-TRIPHOSPHATE / GTP / GTP, エネルギー貯蔵分子*YM
由来	homo sapiens (ヒト) hepacivirus hominis (ウイルス)
キーワード	RIBOSOME / HCV IRES