Structural Insights into the Role of Diphthamide on Elongation Factor 2 in mRNA Reading-Frame Maintenance. Issue 17 (17th August 2018)

• Record Type: Journal Article
• Authors: Pellegrino, Simone; Demeshkina, Natalia; Mancera-Martinez, Eder; Melnikov, Sergey; Simonetti, Angelita; Myasnikov, Alexander; Yusupov, Marat; Yusupova, Gulnara; Hashem, Yaser
• Is Part Of: Journal of molecular biology. Volume 430:Issue 17(2018)
• Page Start: 2677
• Page End: 2687
• Publication Date: 2018-08-17
• Subjects: ribosome translocation -- cryo-EM -- eEF2 -- diphthamide -- reading-frame maintenance; SSU small ribosomal subunit -- LSU large ribosomal subunit -- DC decoding center -- cryo-EM cryo-electron microscopy; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2018.06.006
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: One of the most critical steps of protein biosynthesis is the coupled movement of mRNA, which encodes genetic information, with tRNAs on the ribosome. In eukaryotes, this process is catalyzed by a conserved G-protein, the elongation factor 2 (eEF2), which carries a unique post-translational modification, called diphthamide, found in all eukaryotic species. Here we present near-atomic resolution cryo-electron microscopy structures of yeast 80S ribosome complexes containing mRNA, tRNA and eEF2 trapped in different GTP-hydrolysis states which provide further structural insights into the role of diphthamide in the mechanism of translation fidelity in eukaryotes. Graphical abstract: Unlabelled Image Highlights: Near-atomic resolution structures of 80S/tRNA/mRNA/eEF2 in different hydrolytic states. eEF2 regulates the translocation step and ensures the fidelity of translation. Diphthamide modification might play a pivotal role in mRNA reading-frame maintenance.