Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural insights into the role of eIF3 in translation mediated by the HCV IRES.
Journal, issue, pages	Proc Natl Acad Sci U S A, Vol. 122, Issue 49, Page e2505538122, Year 2025
Publish date	Dec 9, 2025
Authors	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 Abstract	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.
External links	Proc Natl Acad Sci U S A / PubMed:41337487 / PubMed Central
Methods	EM (single particle)
Resolution	3.0 - 3.3 Å
Structure data	62386 9kkf EMDB-62386, PDB-9kkf: Structure of the human 40S ribosome complexed with HCV IRES and eIF3 Method: EM (single particle) / Resolution: 3.3 Å 62453 9kn5 EMDB-62453, PDB-9kn5: Structure of the human 40S ribosome complexed with HCV IRES, eIF1A and eIF3 Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 3.3 Å 62535 9krp EMDB-62535, PDB-9krp: Structure of the HCV IRES-dependent 48S translation initiation complex with eIF5B and eIF3 Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 3.3 Å
Chemicals	ChemComp-ZN: Unknown entry ChemComp-MG: Unknown entry ChemComp-GTP: GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM
Source	homo sapiens (human) hepacivirus hominis
Keywords	RIBOSOME / HCV IRES