SNAP output for PDB entry 8aw3 [SNAP web server]

PDB-id

8aw3; SNAP-derived features in text and JSON formats; DNAproDB

Class

RNA binding protein

Method

cryo-EM (3.6 Å)

Summary

cryo-EM structure of the tb adat2-3 deaminase in complex with trna

Reference

Dolce LG, Zimmer AA, Tengo L, Weis F, Rubio MAT, Alfonzo JD, Kowalinski E (2022): "Structural basis for sequence-independent substrate selection by eukaryotic wobble base tRNA deaminase ADAT2/3." Nat Commun, 13, 6737. doi: 10.1038/s41467-022-34441-z.

Abstract

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.