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Cryo-EM of elongating ribosome with EF-Tu•GTP elucidates tRNA proofreading.
Nature. 2020 Jul 01 [Online ahead of print]Nat

Abstract

Ribosomes accurately decode mRNA by proofreading each aminoacyl-tRNA that is delivered by the elongation factor EF-Tu1. To understand the molecular mechanism of this proofreading step it is necessary to visualize GTP-catalysed elongation, which has remained a challenge2-4. Here we use time-resolved cryogenic electron microscopy to reveal 33 ribosomal states after the delivery of aminoacyl-tRNA by EF-Tu•GTP. Instead of locking cognate tRNA upon initial recognition, the ribosomal decoding centre dynamically monitors codon-anticodon interactions before and after GTP hydrolysis. GTP hydrolysis enables the GTPase domain of EF-Tu to extend away, releasing EF-Tu from tRNA. The 30S subunit then locks cognate tRNA in the decoding centre and rotates, enabling the tRNA to bypass 50S protrusions during accommodation into the peptidyl transferase centre. By contrast, the decoding centre fails to lock near-cognate tRNA, enabling the dissociation of near-cognate tRNA both during initial selection (before GTP hydrolysis) and proofreading (after GTP hydrolysis). These findings reveal structural similarity between ribosomes in initial selection states5,6 and in proofreading states, which together govern the efficient rejection of incorrect tRNA.

Authors+Show Affiliations

RNA Therapeutics Institute, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA.RNA Therapeutics Institute, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA. Central European Institute of Technology, Masaryk University, Brno, Czech Republic.RNA Therapeutics Institute, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA. andrei.korostelev@umassmed.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32612237

Citation

Loveland, Anna B., et al. "Cryo-EM of Elongating Ribosome With EF-Tu•GTP Elucidates tRNA Proofreading." Nature, 2020.
Loveland AB, Demo G, Korostelev AA. Cryo-EM of elongating ribosome with EF-Tu•GTP elucidates tRNA proofreading. Nature. 2020.
Loveland, A. B., Demo, G., & Korostelev, A. A. (2020). Cryo-EM of elongating ribosome with EF-Tu•GTP elucidates tRNA proofreading. Nature. https://doi.org/10.1038/s41586-020-2447-x
Loveland AB, Demo G, Korostelev AA. Cryo-EM of Elongating Ribosome With EF-Tu•GTP Elucidates tRNA Proofreading. Nature. 2020 Jul 1; PubMed PMID: 32612237.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cryo-EM of elongating ribosome with EF-Tu•GTP elucidates tRNA proofreading. AU - Loveland,Anna B, AU - Demo,Gabriel, AU - Korostelev,Andrei A, Y1 - 2020/07/01/ PY - 2019/08/30/received PY - 2020/04/10/accepted PY - 2020/7/3/entrez JF - Nature JO - Nature N2 - Ribosomes accurately decode mRNA by proofreading each aminoacyl-tRNA that is delivered by the elongation factor EF-Tu1. To understand the molecular mechanism of this proofreading step it is necessary to visualize GTP-catalysed elongation, which has remained a challenge2-4. Here we use time-resolved cryogenic electron microscopy to reveal 33 ribosomal states after the delivery of aminoacyl-tRNA by EF-Tu•GTP. Instead of locking cognate tRNA upon initial recognition, the ribosomal decoding centre dynamically monitors codon-anticodon interactions before and after GTP hydrolysis. GTP hydrolysis enables the GTPase domain of EF-Tu to extend away, releasing EF-Tu from tRNA. The 30S subunit then locks cognate tRNA in the decoding centre and rotates, enabling the tRNA to bypass 50S protrusions during accommodation into the peptidyl transferase centre. By contrast, the decoding centre fails to lock near-cognate tRNA, enabling the dissociation of near-cognate tRNA both during initial selection (before GTP hydrolysis) and proofreading (after GTP hydrolysis). These findings reveal structural similarity between ribosomes in initial selection states5,6 and in proofreading states, which together govern the efficient rejection of incorrect tRNA. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/32612237/Cryo-EM_of_elongating_ribosome_with_EF-Tu•GTP_elucidates_tRNA_proofreading L2 - https://doi.org/10.1038/s41586-020-2447-x DB - PRIME DP - Unbound Medicine ER -
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