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Team 6 : Mitochondrial translation and pathologies, 2012-2020

Team leaders : Catherine FLORENTZ & Marie SISSLER


Research topics

  • tRNA databases, tertiary structural network and deep phylogeny (more)
  • Biocrystallogenesis and mt-aaRSs crystal structures (more)
  • Mt-aaRSs of bacterial origin behave differentially from bacterial aaRS (more)
  • Human mt aminoacylation systems and neurodegeneration (more)

Role in MitoCross

First goal

Structure and dynamics of mt-tRNAs, mitochondrial aminoacyl-tRNA synthetases (mt-aaRS), and related proteins: Structural and dynamic properties of mt-tRNAs will be (further) explored and the "mamit" tRNA database will be perpetuated, so that to reveal the limits of structure degeneration of mammalian mt-tRNAs still compatible with translation and to trace back evolutionary history of organelle tRNA species and mt-genome organization. Biophysical and dynamic properties of mt-aaRSs and mitochondria-related proteins will be determined, and their crystallographic structures established.To render this realistic, the N-terminal of the mature proteins existing within mitochondria (deprived of their mitochondrial targeting sequences) will be experimentally determined.

Second goal

New functional properties and evolution of human mitochondrial systems: Not much is known on the in vivo status of mt-aaRSs. the sub-mitochondrial organization and partners of these enzymes will be established and their influence on activity tested. In order to decipher specific adaptation signals of aaRSs of either bacterial or eukaryal origin to the mitochondrial environment, and accordingly, the refined evolutionary histories of mt-aaRSs, a bioinformatic study on aaRSs is being developped.

Third goal

Molecular defects in mt-tRNAs/aaRSs neurogenerative disorders: The incidence of point mutations (either pathology-related or neutral polymorphisms) on mt-tRNA structure and stability will be evaluated. Mutant mt-aaRSs will be characterized, under functional, biochemical, biophysical and/or structural aspects. Also, the effect of pathology-related mutations will be considered on newly-established mt-aaRS partnership and/or sub-mitochondrial organization.


Members

Former members



Useful link

Compilation of mammalian mitochondrial tRNA genes: the mamit tRNA database

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