6ip8 | pdb_00006ip8
Cryo-EM structure of the HCV IRES dependently initiated CMV-stalled 80S ribosome (Structure iv)
Structural highlights
FunctionERF1_HUMAN Directs the termination of nascent peptide synthesis (translation) in response to the termination codons UAA, UAG and UGA. Component of the transient SURF complex which recruits UPF1 to stalled ribosomes in the context of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons.[1] Publication Abstract from PubMedTranslation 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. HCV IRES Captures an Actively Translating 80S Ribosome.,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 Mol Cell. 2019 May 7. pii: S1097-2765(19)30314-4. doi:, 10.1016/j.molcel.2019.04.022. PMID:31080011[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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