IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-40404-9.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-40404-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-40404-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. 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.
    3. 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.
    4. 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.
    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. 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.
    7. 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.
    8. 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.
    9. 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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Sakshi Jain & Lukasz Koziej & Panagiotis Poulis & Igor Kaczmarczyk & Monika Gaik & Michal Rawski & Namit Ranjan & Sebastian Glatt & Marina V. Rodnina, 2023. "Modulation of translational decoding by m6A modification of mRNA," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Simon A. Fromm & Kate M. O’Connor & Michael Purdy & Pramod R. Bhatt & Gary Loughran & John F. Atkins & Ahmad Jomaa & Simone Mattei, 2023. "The translating bacterial ribosome at 1.55 Å resolution generated by cryo-EM imaging services," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    3. Christine E. Carbone & Anna B. Loveland & Howard B. Gamper & Ya-Ming Hou & Gabriel Demo & Andrei A. Korostelev, 2021. "Time-resolved cryo-EM visualizes ribosomal translocation with EF-G and GTP," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    4. Narayan Prasad Parajuli & Andrew Emmerich & Chandra Sekhar Mandava & Michael Y. Pavlov & Suparna Sanyal, 2023. "Antibiotic thermorubin tethers ribosomal subunits and impedes A-site interactions to perturb protein synthesis in bacteria," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Juntaek Oh & Zelin Shan & Shuichi Hoshika & Jun Xu & Jenny Chong & Steven A. Benner & Dmitry Lyumkis & Dong Wang, 2023. "A unified Watson-Crick geometry drives transcription of six-letter expanded DNA alphabets by E. coli RNA polymerase," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    6. Valentyn Petrychenko & Bee-Zen Peng & Ana C. A. P. Schwarzer & Frank Peske & Marina V. Rodnina & Niels Fischer, 2021. "Structural mechanism of GTPase-powered ribosome-tRNA movement," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    7. Timo Flügel & Magdalena Schacherl & Anett Unbehaun & Birgit Schroeer & Marylena Dabrowski & Jörg Bürger & Thorsten Mielke & Thiemo Sprink & Christoph A. Diebolder & Yollete V. Guillén Schlippe & Chris, 2024. "Transient disome complex formation in native polysomes during ongoing protein synthesis captured by cryo-EM," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    8. Michael F. Fuss & Jan-Philip Wieferig & Robin A. Corey & Yvonne Hellmich & Igor Tascón & Joana S. Sousa & Phillip J. Stansfeld & Janet Vonck & Inga Hänelt, 2023. "Cyclic di-AMP traps proton-coupled K+ transporters of the KUP family in an inward-occluded conformation," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    9. Chris H. Hill & Lukas Pekarek & Sawsan Napthine & Anuja Kibe & Andrew E. Firth & Stephen C. Graham & Neva Caliskan & Ian Brierley, 2021. "Structural and molecular basis for Cardiovirus 2A protein as a viral gene expression switch," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    10. Panagiotis Poulis & Anoshi Patel & Marina V. Rodnina & Sarah Adio, 2022. "Altered tRNA dynamics during translocation on slippery mRNA as determinant of spontaneous ribosome frameshifting," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    11. Markus Hillmeier & Mirko Wagner & Timm Ensfelder & Eva Korytiakova & Peter Thumbs & Markus Müller & Thomas Carell, 2021. "Synthesis and structure elucidation of the human tRNA nucleoside mannosyl-queuosine," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    12. Ritwika S. Basu & Michael B. Sherman & Matthieu G. Gagnon, 2022. "Compact IF2 allows initiator tRNA accommodation into the P site and gates the ribosome to elongation," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    13. Lars V. Bock & Helmut Grubmüller, 2022. "Effects of cryo-EM cooling on structural ensembles," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    14. Mirjana Malnar Črnigoj & Urša Čerček & Xiaoke Yin & Manh Tin Ho & Barbka Repic Lampret & Manuela Neumann & Andreas Hermann & Guy Rouleau & Beat Suter & Manuel Mayr & Boris Rogelj, 2023. "Phenylalanine-tRNA aminoacylation is compromised by ALS/FTD-associated C9orf72 C4G2 repeat RNA," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    15. K. Shanmugha Rajan & Hava Madmoni & Anat Bashan & Masato Taoka & Saurav Aryal & Yuko Nobe & Tirza Doniger & Beathrice Galili Kostin & Amit Blumberg & Smadar Cohen-Chalamish & Schraga Schwartz & Andre , 2023. "A single pseudouridine on rRNA regulates ribosome structure and function in the mammalian parasite Trypanosoma brucei," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    16. Joonas A. Jamsen & David D. Shock & Samuel H. Wilson, 2022. "Watching right and wrong nucleotide insertion captures hidden polymerase fidelity checkpoints," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    17. Caillan Crowe-McAuliffe & Victoriia Murina & Kathryn Jane Turnbull & Susanne Huch & Marje Kasari & Hiraku Takada & Lilit Nersisyan & Arnfinn Sundsfjord & Kristin Hegstad & Gemma C. Atkinson & Vicent P, 2022. "Structural basis for PoxtA-mediated resistance to phenicol and oxazolidinone antibiotics," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    18. Jana Aupič & Jure Borišek & Sebastian M. Fica & Wojciech P. Galej & Alessandra Magistrato, 2023. "Monovalent metal ion binding promotes the first transesterification reaction in the spliceosome," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    19. Savannah M. Seely & Narayan P. Parajuli & Arindam Tarafder & Xueliang Ge & Suparna Sanyal & Matthieu G. Gagnon, 2023. "Molecular basis of the pleiotropic effects by the antibiotic amikacin on the ribosome," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    20. Ana Rita D Araújo & Tânia Melo & Elisabete A Maciel & Clara Pereira & Catarina M Morais & Deolinda R Santinha & Joana F Tavares & Helena Oliveira & Amália S Jurado & Vítor Costa & Pedro Domingues & Ma, 2018. "Errors in protein synthesis increase the level of saturated fatty acids and affect the overall lipid profiles of yeast," PLOS ONE, Public Library of Science, vol. 13(8), pages 1-28, August.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40404-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.