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Our team is mainly focusing on large macromolecular assemblies involved in translation initiation. We use X-ray crystallography, SAXS and cryo-EM to perform our structural studies and we also develop biochemical strategies for our functional studies.


Main collaborations :

  • Wolfgang Seufert (University of Regensburg, Germany)
  • SOLEIL Synchrotron (TREMTI project supported by ANR)
  • Anh Tuân Phan (NTU, Singapore)
  • Philippe Marlière (Heurisko INC, USA) and Valérie Pezo (ISSB, Evry)


Translation initiation mechanisms

Mechanisms for identification of the correct start codon display strong similarities in eukaryotes and archaea. In particular, 3 factors, e/aIF1 (eukaryotic/archaeal initiation factor 1), e/aIF1A and e/aIF2, together with methionyl initiator tRNA (Met-tRNAiMet), mRNA and the small ribosomal subunit form the core of a pre-initiation complex (PIC) controlling translation initiation accuracy. In archaea, translation initiation does not imply long-range scanning of mRNA like in eukaryotes. Instead, the ribosome is pre-positioned thanks to Shine-Dalgarno sequences or to very short 5’ untranslated regions. However, we propose that detection of the start codon proceeds through local scanning by the core PIC within a short mRNA region. Thus, study of archaeal initiation is of general interest not only per se but also because it can provide new useful information on eukaryotic systems. For instance, our crystal structure of the archaeal version of the aIF2-GDPNP-Met-tRNAi ternary complex (TC) has been used to model eIF2 in the cryo-EM maps of eukaryotic complexes.

Crystal Structure of aIF2 and of the ternary complex aIF2-GDPNP-tRNA (Yatime et al., 2007, PNAS, Schmitt et al., 2012 Nat. Struct. Mol. Biol.)

We reconstituted in vitro the full archaeal PIC using Pyrococcus abyssi components and determined its structure using cryo-EM. After 3D classifications, two distinct structures were obtained showing two conformational states of the TC. In the first state, the TC is bound to the ribosome in a relaxed conformation with the tRNA oriented out of the P site. In the second state, the tRNA is accommodated within the P site and the TC becomes constrained. If a start codon is present at the P site, base pairing with the tRNA anticodon compensates for the constraint. In the absence of a start codon, aIF2 contributes to swing out the tRNA. This spring force concept highlights a mechanism of codon/anticodon probing by the initiator tRNA directly assisted by aIF2.