| RRC ID |
59707
|
| 著者 |
Yokoyama T, Machida K, Iwasaki W, Shigeta T, Nishimoto M, Takahashi M, Sakamoto A, Yonemochi M, Harada Y, Shigematsu H, Shirouzu M, Tadakuma H, Imataka H, Ito T.
|
| タイトル |
HCV IRES Captures an Actively Translating 80S Ribosome.
|
| ジャーナル |
Mol Cell
|
| Abstract |
Translation initiation of hepatitis C virus (HCV) genomic RNA is induced by an internal ribosome entry site (IRES). Our cryoelectron microscopy (cryo-EM) analysis revealed that the HCV IRES binds to the solvent side of the 40S platform of the cap-dependently translating 80S ribosome. Furthermore, we obtained the cryo-EM structures of the HCV IRES capturing the 40S subunit of the IRES-dependently translating 80S ribosome. In the elucidated structures, the HCV IRES "body," consisting of domain III except for subdomain IIIb, binds to the 40S subunit, while the "long arm," consisting of domain II, remains flexible and does not impede the ongoing translation. Biochemical experiments revealed that the cap-dependently translating ribosome becomes a better substrate for the HCV IRES than the free ribosome. Therefore, the HCV IRES is likely to efficiently induce the translation initiation of its downstream mRNA with the captured translating ribosome as soon as the ongoing translation terminates.
|
| 巻・号 |
74(6)
|
| ページ |
1205-1214.e8
|
| 公開日 |
2019-6-20
|
| DOI |
10.1016/j.molcel.2019.04.022
|
| PII |
S1097-2765(19)30314-4
|
| PMID |
31080011
|
| MeSH |
Binding Sites
Cryoelectron Microscopy
Eukaryotic Initiation Factors / chemistry*
Eukaryotic Initiation Factors / genetics
Eukaryotic Initiation Factors / metabolism
HEK293 Cells
Hepacivirus / genetics*
Hepacivirus / metabolism
Host-Pathogen Interactions
Humans
Internal Ribosome Entry Sites
Models, Molecular
Nucleic Acid Conformation
Peptide Chain Initiation, Translational*
RNA, Viral / chemistry*
RNA, Viral / genetics
RNA, Viral / metabolism
Ribosome Subunits, Large, Eukaryotic / genetics
Ribosome Subunits, Large, Eukaryotic / metabolism
Ribosome Subunits, Large, Eukaryotic / ultrastructure*
Ribosome Subunits, Small, Eukaryotic / genetics
Ribosome Subunits, Small, Eukaryotic / metabolism
Ribosome Subunits, Small, Eukaryotic / ultrastructure*
|
| IF |
14.548
|
| 引用数 |
5
|
| リソース情報 |
| ヒト・動物細胞 |
293T(RCB2202) |
