7nz9 | pdb_00007nz9
Crystal structure of mouse ADAT2/ADAT3 tRNA deamination complex V128L mutant
Structural highlights
FunctionADAT2_MOUSE Probably participates in deamination of adenosine-34 to inosine in many tRNAs. Publication Abstract from PubMedPost-transcriptional modification of tRNA wobble adenosine into inosine is crucial for decoding multiple mRNA codons by a single tRNA. The eukaryotic wobble adenosine-to-inosine modification is catalysed by the ADAT (ADAT2/ADAT3) complex that modifies up to eight tRNAs, requiring a full tRNA for activity. Yet, ADAT catalytic mechanism and its implication in neurodevelopmental disorders remain poorly understood. Here, we have characterized mouse ADAT and provide the molecular basis for tRNAs deamination by ADAT2 as well as ADAT3 inactivation by loss of catalytic and tRNA-binding determinants. We show that tRNA binding and deamination can vary depending on the cognate tRNA but absolutely rely on the eukaryote-specific ADAT3 N-terminal domain. This domain can rotate with respect to the ADAT catalytic domain to present and position the tRNA anticodon-stem-loop correctly in ADAT2 active site. A founder mutation in the ADAT3 N-terminal domain, which causes intellectual disability, does not affect tRNA binding despite the structural changes it induces but most likely hinders optimal presentation of the tRNA anticodon-stem-loop to ADAT2. The structure of the mouse ADAT2/ADAT3 complex reveals the molecular basis for mammalian tRNA wobble adenosine-to-inosine deamination.,Ramos-Morales E, Bayam E, Del-Pozo-Rodriguez J, Salinas-Giege T, Marek M, Tilly P, Wolff P, Troesch E, Ennifar E, Drouard L, Godin JD, Romier C Nucleic Acids Res. 2021 Jun 21;49(11):6529-6548. doi: 10.1093/nar/gkab436. PMID:34057470[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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