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Geometric alignment of aminoacyl-tRNA relative to catalytic centers of the ribosome underpins accurate mRNA decoding

Author

Listed:
  • Dylan Girodat

    (Los Alamos National Laboratory
    University of Arkansas)

  • Hans-Joachim Wieden

    (University of Manitoba)

  • Scott C. Blanchard

    (St. Jude Children’s Research Hospital)

  • Karissa Y. Sanbonmatsu

    (Los Alamos National Laboratory
    New Mexico Consortium)

Abstract

Accurate protein synthesis is determined by the two-subunit ribosome’s capacity to selectively incorporate cognate aminoacyl-tRNA for each mRNA codon. The molecular basis of tRNA selection accuracy, and how fidelity can be affected by antibiotics, remains incompletely understood. Using molecular simulations, we find that cognate and near-cognate tRNAs delivered to the ribosome by Elongation Factor Tu (EF-Tu) can follow divergent pathways of motion into the ribosome during both initial selection and proofreading. Consequently, cognate aa-tRNAs follow pathways aligned with the catalytic GTPase and peptidyltransferase centers of the large subunit, while near-cognate aa-tRNAs follow pathways that are misaligned. These findings suggest that differences in mRNA codon-tRNA anticodon interactions within the small subunit decoding center, where codon-anticodon interactions occur, are geometrically amplified over distance, as a result of this site’s physical separation from the large ribosomal subunit catalytic centers. These insights posit that the physical size of both tRNA and ribosome are key determinants of the tRNA selection fidelity mechanism.

Suggested Citation

  • Dylan Girodat & Hans-Joachim Wieden & Scott C. Blanchard & Karissa Y. Sanbonmatsu, 2023. "Geometric alignment of aminoacyl-tRNA relative to catalytic centers of the ribosome underpins accurate mRNA decoding," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40404-9
    DOI: 10.1038/s41467-023-40404-9
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    References listed on IDEAS

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    1. Alexey Rozov & Iskander Khusainov & Kamel El Omari & Ramona Duman & Vitaliy Mykhaylyk & Marat Yusupov & Eric Westhof & Armin Wagner & Gulnara Yusupova, 2019. "Importance of potassium ions for ribosome structure and function revealed by long-wavelength X-ray diffraction," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    2. Jeong Woong Lee & Kirk Beebe & Leslie A. Nangle & Jaeseon Jang & Chantal M. Longo-Guess & Susan A. Cook & Muriel T. Davisson & John P. Sundberg & Paul Schimmel & Susan L. Ackerman, 2006. "Editing-defective tRNA synthetase causes protein misfolding and neurodegeneration," Nature, Nature, vol. 443(7107), pages 50-55, September.
    3. Michael R. Wasserman & Arto Pulk & Zhou Zhou & Roger B. Altman & John C. Zinder & Keith D. Green & Sylvie Garneau-Tsodikova & Jamie H. Doudna Cate & Scott C. Blanchard, 2015. "Chemically related 4,5-linked aminoglycoside antibiotics drive subunit rotation in opposite directions," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    4. Emily J. Rundlet & Mikael Holm & Magdalena Schacherl & S. Kundhavai Natchiar & Roger B. Altman & Christian M. T. Spahn & Alexander G. Myasnikov & Scott C. Blanchard, 2021. "Structural basis of early translocation events on the ribosome," Nature, Nature, vol. 595(7869), pages 741-745, July.
    5. Anna B. Loveland & Gabriel Demo & Andrei A. Korostelev, 2020. "Cryo-EM of elongating ribosome with EF-Tu•GTP elucidates tRNA proofreading," Nature, Nature, vol. 584(7822), pages 640-645, August.
    6. Natalia Demeshkina & Lasse Jenner & Eric Westhof & Marat Yusupov & Gulnara Yusupova, 2012. "A new understanding of the decoding principle on the ribosome," Nature, Nature, vol. 484(7393), pages 256-259, April.
    7. Hasan Demirci & Frank Murphy & Eileen Murphy & Steven T. Gregory & Albert E. Dahlberg & Gerwald Jogl, 2013. "A structural basis for streptomycin-induced misreading of the genetic code," Nature Communications, Nature, vol. 4(1), pages 1-8, June.
    8. Alexey Rozov & Natalia Demeshkina & Eric Westhof & Marat Yusupov & Gulnara Yusupova, 2015. "Structural insights into the translational infidelity mechanism," Nature Communications, Nature, vol. 6(1), pages 1-9, November.
    9. Alexey Rozov & Natalia Demeshkina & Iskander Khusainov & Eric Westhof & Marat Yusupov & Gulnara Yusupova, 2016. "Novel base-pairing interactions at the tRNA wobble position crucial for accurate reading of the genetic code," Nature Communications, Nature, vol. 7(1), pages 1-10, April.
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