The structure of the mouse ADAT2/ADAT3 complex reveals the
molecular basis for mammalian tRNA wobble adenosine-to-inosine
deamination

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The structure of the mouse ADAT2/ADAT3 complex reveals the molecular basis for mammalian tRNA ...

Přehled o publikaci

J 2021

The structure of the mouse ADAT2/ADAT3 complex reveals the molecular basis for mammalian tRNA wobble adenosine-to-inosine deamination

RAMOS-MORALES, Elizabeth; Efil BAYAM; Jordi DEL-POZO-RODRIGUEZ; Thalia SALINAS-GIEGE; Martin MAREK et. al.

Basic information

Original name

The structure of the mouse ADAT2/ADAT3 complex reveals the molecular basis for mammalian tRNA wobble adenosine-to-inosine deamination

Authors

Edition

Nucleic Acids Research, Oxford, Oxford University Press, 2021, 0305-1048

Other information

Language

English

Type of outcome

Article in a journal

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Organization

Přírodovědecká fakulta – Repository – Repository

DOI

http://dx.doi.org/10.1093/nar/gkab436

UT WoS

000671550100040

EID Scopus

2-s2.0-85109114883

Keywords in English

CRYSTAL-STRUCTURE; INTELLECTUAL DISABILITY; ESCHERICHIA-COLI; TADA; ANTICODON; SPECIFICITY; POSITION; FEATURES; DATABASE; ENZYMES

Changed: 5/2/2022 02:10, RNDr. Daniel Jakubík

Abstract

V originále

Post-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.

Files attached

https://is.muni.cz/publication/1831398/1831398.pdf

Cite

RAMOS-MORALES, Elizabeth; Efil BAYAM; Jordi DEL-POZO-RODRIGUEZ; Thalia SALINAS-GIEGE; Martin MAREK; Ramos-Morales, E (Ramos- TILLY; Philippe WOLFF; Edouard TROESCH; Eric ENNIFAR; Laurence DROUARD; Juliette D. GODIN and Christophe ROMIER. The structure of the mouse ADAT2/ADAT3 complex reveals the molecular basis for mammalian tRNA wobble adenosine-to-inosine deamination. Nucleic Acids Research. Oxford: Oxford University Press, 2021, vol. 49, No 11, p. 6529-6548. ISSN 0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkab436.

@article{48514,
   author = {RamosandMorales, Elizabeth and Bayam, Efil and DelandPozoandRodriguez, Jordi and SalinasandGiege, Thalia and Marek, Martin and Tilly, RamosandMorales, E (Ramosand and Wolff, Philippe and Troesch, Edouard and Ennifar, Eric and Drouard, Laurence and Godin, Juliette D. and Romier, Christophe},
   article_location = {Oxford},
   article_number = {11},
   doi = {http://dx.doi.org/10.1093/nar/gkab436},
   keywords = {CRYSTAL-STRUCTURE; INTELLECTUAL DISABILITY; ESCHERICHIA-COLI; TADA; ANTICODON; SPECIFICITY; POSITION; FEATURES; DATABASE; ENZYMES},
   language = {eng},
   issn = {0305-1048},
   journal = {Nucleic Acids Research},
   title = {The structure of the mouse ADAT2/ADAT3 complex reveals the molecular basis for mammalian tRNA wobble adenosine-to-inosine deamination},
   url = {https://academic.oup.com/nar/article/49/11/6529/6290083},
   volume = {49},
   year = {2021}
}

TY  - JOUR
ID  - 48514
AU  - Ramos-Morales, Elizabeth - Bayam, Efil - Del-Pozo-Rodriguez, Jordi - Salinas-Giege, Thalia - Marek, Martin - Tilly, Ramos-Morales, E (Ramos- - Wolff, Philippe - Troesch, Edouard - Ennifar, Eric - Drouard, Laurence - Godin, Juliette D. - Romier, Christophe
PY  - 2021
TI  - The structure of the mouse ADAT2/ADAT3 complex reveals the molecular basis for mammalian tRNA wobble adenosine-to-inosine deamination
JF  - Nucleic Acids Research
VL  - 49
IS  - 11
SP  - 6529-6548
EP  - 6529-6548
PB  - Oxford University Press
SN  - 0305-1048
KW  - CRYSTAL-STRUCTURE
KW  - INTELLECTUAL DISABILITY
KW  - ESCHERICHIA-COLI
KW  - TADA
KW  - ANTICODON
KW  - SPECIFICITY
KW  - POSITION
KW  - FEATURES
KW  - DATABASE
KW  - ENZYMES
UR  - https://academic.oup.com/nar/article/49/11/6529/6290083
N2  - Post-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.
ER  -

RAMOS-MORALES, Elizabeth; Efil BAYAM; Jordi DEL-POZO-RODRIGUEZ; Thalia SALINAS-GIEGE; Martin MAREK; Ramos-Morales, E (Ramos- TILLY; Philippe WOLFF; Edouard TROESCH; Eric ENNIFAR; Laurence DROUARD; Juliette D. GODIN and Christophe ROMIER. The structure of the mouse ADAT2/ADAT3 complex reveals the molecular basis for mammalian tRNA wobble adenosine-to-inosine deamination. \textit{Nucleic Acids Research}. Oxford: Oxford University Press, 2021, vol.~49, No~11, p.~6529-6548. ISSN~0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkab436.