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TitleHCV IRES Captures an Actively Translating 80S Ribosome.
Journal, issue, pagesMol Cell, Vol. 74, Issue 6, Page 1205-11214.e8, Year 2019
Publish dateJun 20, 2019
AuthorsTakeshi Yokoyama / Kodai Machida / Wakana Iwasaki / Tomoaki Shigeta / Madoka Nishimoto / Mari Takahashi / Ayako Sakamoto / Mayumi Yonemochi / Yoshie Harada / Hideki Shigematsu / Mikako Shirouzu / Hisashi Tadakuma / Hiroaki Imataka / Takuhiro Ito /
PubMed AbstractTranslation 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 ...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.
External linksMol Cell / PubMed:31080011
MethodsEM (single particle)
Resolution3.9 - 4.6 Å
Structure data

EMDB-9699:
Cryo-EM structure of the CMV-stalled human 80S ribosome (Structure i)
Method: EM (single particle) / Resolution: 4.5 Å

EMDB-9701, PDB-6ip5:
Cryo-EM structure of the CMV-stalled human 80S ribosome (Structure ii)
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-9702, PDB-6ip6:
Cryo-EM structure of the CMV-stalled human 80S ribosome with HCV IRES (Structure iii)
Method: EM (single particle) / Resolution: 4.5 Å

EMDB-9703, PDB-6ip8:
Cryo-EM structure of the HCV IRES dependently initiated CMV-stalled 80S ribosome (Structure iv)
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-9704:
Cryo-EM structure of the HCV IRES dependently initiated CMV-stalled 80S ribosome, rotated (Structure v)
Method: EM (single particle) / Resolution: 4.6 Å

Source
  • homo sapiens (human)
  • Human (human)
KeywordsRIBOSOME / Translation

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