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Accueil > Départements > Biochimie, Biophysique et Biologie Structurale > Herman VAN TILBEURGH : Fonction et Architecture des Assemblages Macromoléculaires

Analyse moléculaire de la modification T6a ARNt universel

Principal investigators : Herman van Tilbeurgh, Dominique Liger & Bruno Collinet

Version françaises en cours

Collaborations

D. Libri (Institut Jacques Monod, Paris)
T. Basta (I2BC, Microbiology Department)

Project

The N6-threonylcarbamoyl adenosine modification (t6A) is one of the few universally conserved tRNA modifications. It adds a threonylcarbamoyl moiety on position 37 of tRNAs that read 5’-ANN-3’ codons. In vivo, t6A is important for start codon recognition and reading frame maintenance. The t6A system mobilizes partially different sets of proteins in bacteria on the one hand and archaea/eukaryotes on the other. In E. coli, apart from YgjD (=Kae1) and YrdC (=Sua5) two more proteins are essential for the t6A modification : YjeE and YeaZ. In archaea and eukaryotes, Kae1 is part of a stable multiprotein complex KEOPS, together with three other proteins : Bud32, Pcc1 and Cgi121. Although the necessary t6A proteins have been identified for the three domains of life, their respective role and mechanism in the modification are not well understood. The main objective of this project is to unravel the molecular/mechanistic aspects of the t6A system in E. coli, S. cerevisiae and P. abyssi using biochemical analysis, protein-protein interaction studies and crystallography.

t6A tRNA modification
Overall reaction scheme of the t6A tRNA modification which proceeds in two steps
Model of the complete Yeast KEOPS complex
Based on structures of subcomplexes
(Gon7 ; green, Pcc1 pink ; Kae1, red ; Bud32, blue ; Cgi121, yellow)

References

- Crystal structures of the Gon7/Pcc1 and Bud32/Cgi121 complexes provide a model for the complete yeast KEOPS complex. Zhang, W, Collinet, B, Graille, M, Daugeron, M-C, Lazar, N., Libri, D., Durand, D. and van Tilbeurgh, H. Nucleic Acids Res. 2015, in press

- The ATP-mediated formation of the YgjD-YeaZ-YjeE complex is required for the biosynthesis of tRNA t6A in Escherichia coli. Zhang W, Collinet B, Perrochia L, Durand D, van Tilbeurgh H. Nucleic Acids Res. 2015 Feb 18 ;43(3):1804-17.

- In vitro biosynthesis of a universal t6A tRNA modification in Archaea and Eukarya.
Perrochia L, Crozat E, Hecker A, Zhang W, Bareille J, Collinet B, van Tilbeurgh H, Forterre P, Basta T. Nucleic Acids Res. 2013 Feb 1 ;41(3):1953-64.

- Gcn4 misregulation reveals a direct role for the evolutionary conserved EKC/KEOPS in the t6A modification of tRNAs. Daugeron MC, Lenstra TL, Frizzarin M, El Yacoubi B, Liu X, Baudin-Baillieu A, Lijnzaad P, Decourty L, Saveanu C, Jacquier A, Holstege FC, de Crécy-Lagard V, van Tilbeurgh H, Libri D. Nucleic Acids Res. 2011 Aug ;39(14):6148-60.

- Structure of the archaeal Kae1/Bud32 fusion protein MJ1130 : a model for the eukaryotic EKC/KEOPS subcomplex. Hecker A, Lopreiato R, Graille M, Collinet B, Forterre P, Libri D, van Tilbeurgh H. EMBO J. 2008 Sep 3 ;27(17):2340-51.

- An archaeal orthologue of the universal protein Kae1 is an iron metalloprotein which exhibits atypical DNAbinding properties and apurinic-endonuclease activity in vitro. Hecker A, Leulliot N, Gadelle D, Graille M, Justome A, Dorlet P, Brochier C, Quevillon-Cheruel S, Le Cam E, van Tilbeurgh H, Forterre P. Nucleic Acids Res. 007 ;35(18):6042-51.

Contacts


VAN TILBEURGH Herman [Professeur - UPSud]
Equipe Van Tilbeurgh H. - Fonction et Architecture des Assemblages Macromoléculaires [Responsable]
Cristallisation [Responsable Scientifique]
01 69 15 31 55 Orsay - Bât 430


LIGER Dominique [Maitre de conférences - UPSud]
Equipe Van Tilbeurgh H. - Fonction et Architecture des Assemblages Macromoléculaires
01 69 15 79 68 Orsay - Bât 430


COLLINET Bruno [Maitre de conférences - UPMC]
Equipe Van Tilbeurgh H. - Fonction et Architecture des Assemblages Macromoléculaires
01 69 15 79 68 Orsay - Bât 430

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