@article {47465,
	title = {Ensemble cryo-EM uncovers inchworm-like translocation of a viral IRES through the ribosome.},
	journal = {eLife},
	volume = {5},
	year = {2016},
	month = {2016 May 9},
	abstract = {<p>Internal ribosome entry sites (IRESs) mediate cap-independent translation of viral mRNAs. Using electron cryo-microscopy of a single specimen, we present five ribosome structures formed with the Taura syndrome virus IRES and translocase eEF2{\textbullet}GTP bound with sordarin. The structures suggest a trajectory of IRES translocation, required for translation initiation, and provide an unprecedented view of eEF2 dynamics. The IRES rearranges from extended to bent to extended conformations. This inchworm-like movement is coupled with ribosomal inter-subunit rotation and 40S head swivel. eEF2, attached to the 60S subunit, slides along the rotating 40S subunit to enter the A site. Its diphthamide-bearing tip at domain IV separates the tRNA-mRNA-like pseudoknot I (PKI) of the IRES from the decoding center. This unlocks 40S domains, facilitating head swivel and biasing IRES translocation via hitherto-elusive intermediates with PKI captured between the A and P sites. The structures suggest missing links in our understanding of tRNA translocation.</p>
},
	issn = {2050-084X},
	doi = {10.7554/eLife.14874},
	author = {Abeyrathne, Priyanka D and Koh, Cha San and Grant, Timothy and Grigorieff, Nikolaus and Korostelev, Andrei A}
}
@article {65021,
	title = {Taura syndrome virus IRES initiates translation by binding its tRNA-mRNA-like structural element in the ribosomal decoding center.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {111},
	year = {2014},
	month = {2014 Jun 24},
	pages = {9139-44},
	abstract = {<p>In cap-dependent translation initiation, the open reading frame (ORF) of mRNA is established by the placement of the AUG start codon and initiator tRNA in the ribosomal peptidyl (P) site. Internal ribosome entry sites (IRESs) promote translation of mRNAs in a cap-independent manner. We report two structures of the ribosome-bound Taura syndrome virus (TSV) IRES belonging to the family of Dicistroviridae intergenic IRESs. Intersubunit rotational states differ in these structures, suggesting that ribosome dynamics play a role in IRES translocation. Pseudoknot I of the IRES occupies the ribosomal decoding center at the aminoacyl (A) site in a manner resembling that of the tRNA anticodon-mRNA codon. The structures reveal that the TSV IRES initiates translation by a previously unseen mechanism, which is conceptually distinct from initiator tRNA-dependent mechanisms. Specifically, the ORF of the IRES-driven mRNA is established by the placement of the preceding tRNA-mRNA-like structure in the A site, whereas the 40S P site remains unoccupied during this initial step.</p>
},
	keywords = {Nucleic Acid Conformation, Open Reading Frames, Peptide Chain Initiation, Translational, Picornaviridae, Ribosomes, RNA, Messenger, RNA, Transfer, RNA, Viral},
	issn = {1091-6490},
	doi = {10.1073/pnas.1406335111},
	author = {Koh, Cha San and Brilot, Axel F and Grigorieff, Nikolaus and Korostelev, Andrei A}
}
