EMBL, Grenoble "Structural basis for sequence-independent substracte selection by eukaryotic wobble base tRNA deaminase ADAT2/3"
Nature Communication2022, 13, 6737 https://doi.org/10.1038/s41467-022-34441-z
Dolce L.G., Zimmer A.A., Tengo L., Weis F., Rubio M.A.T., Alfonzo J.D. & Kowalinski E.
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Luciano Dolce is a 31 year-old structural biologist. He is interested in RNA editing and modification, with a focus on the protein complexes that perform and regulate them. He did his PhD in Brazil, at the LNBio - Laboratório Nacional de Biociências, applying crystallography and biophysical techniques to study protein-protein complexes. After his PhD, he moved to Grenoble to work as a postdoctoral fellow in Eva Kowalinski's group at EMBL, where he uses Cryo-electron microscopy to better understand RNA editing and modifications in the parasite Trypanosoma brucei.
Contact
Luciano DOLCE
71 avenue des Martyrs
38000 Grenoble
twitter @LgDolce
Résumé de l'article
The essential deamination of adenosine A34 to inosine at the wobble base is the individual tRNA modification with the greatest effects on mRNA decoding, empowering a single tRNA to translate three different codons. To date, many aspects of how eukaryotic deaminases specifically select their multiple substrates remain unclear. Here, using cryo-EM, we present the structure of a eukaryotic ADAT2/3 deaminase bound to a full-length tRNA, revealing that the enzyme distorts the anticodon loop, but in contrast to the bacterial enzymes, selects its substrate via sequence-independent contacts of eukaryote-acquired flexible or intrinsically unfolded motifs distal from the conserved catalytic core. A gating mechanism for substrate entry to the active site is identified. Our multi-step tRNA recognition model yields insights into how RNA editing by A34 deamination evolved, shaped the genetic code, and directly impacts the eukaryotic proteome.
