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Institut de Biologie StructuraleGrenoble / France

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Presentation of the Extremophiles and Large Molecular Assemblies Group

Group leader: Bruno Franzetti


Overview

Extremophilic Archaea are microbes adapted to extreme conditions of salt, temperature and pressure. Their proteins possess unique properties of stability and their cellular machines are often surrogates of eukaryotes. These properties can be harnessed for the purpose of determining the structure and function of large molecular edifices while avoiding the instability and complexity of eukaryotic systems. To fulfil this goal, the ELMA group is developing novel integrated structural biology approaches that use extreme conditions of pressure and temperatures.
The molecular machines of interest are identified from archaeal cells, purified and biochemically characterized in the group. We specialize on chaperones and protease cellular machines that represent interesting targets in biomedicine and help extremophiles to cope with their hostile environments. We are also comparing the biophysical and biochemical properties of homologous enzymes from different types of extremophilic organisms to understand the adaptative evolution of life and to identify the biophysical properties underlying the function of proteins.
Part of our research consists in developing biotechnological processes related to the unique catalytic and physical properties of extremophilic enzymes.

Permanent Staff :

  • Bruno Franzetti (CNRS - DR2)
  • Dominique Madern (CNRS - IR HC)
  • Eric Girard (CEA staff scientist)
  • Frank Gabel (CEA staff scientist)
  • Pierre Vauclare (CNRS - CR1)
  • Giuseppe Zaccaï (CNRS - DR1 emeritus)
  • Jacques Coves (CNRS - DR2)

Post-doctoral scientists:

  • Gaëlle Hogrel (CNRS postdoc)
  • Alexandre Appolaire (CNRS "ingénieur")
  • Alexandra Crete (CEA technician)

PhD Students :

  • Emilie Mahieu
  • Sylvain Engilberge

Research topics

  • Molecular adaptation and evolution in extreme environments : Life in the deep sea and in hypersaline lakes.
  • Fundamental cellular processes in the third kingdom of life : proteolysis and protein quality control in Archaea.
  • Developments in structural biology : small-angle scattering, high pressure and experimental phasing
  • Biotechnologies of extremophiles

Key words

Protein dynamics and mechanisms. Macromolecular Nanomachines. Biocatalysis and enzymatic chemistry. Methodological developments. Extremophiles. Archaea. Extreme Environments. Molecular Adaptation and Evolution of Life. Habitability. Stress Response. Deep sea. Pressure. Halophiles. Thermophiles. Piezophiles. Malate dehydrogenase. Proteolysis. Proteasome. Chaperones. TET peptidase. ...

Specialized techniques

  • Microbiology of Archaea: Halophilic Archaea cultivation, molecular biology and genetics. Archaeal cell biology. Subcellular proteomics from Archaeal cells. Genetics in halophiles
  • Extremophiles Biochemistry: Thermophilic protein complexes purification. Halophilic protein purification. Proteases and chaperone biochemistry. Enzymology in extreme conditions.
  • Advanced Crystallography: Protein crystallisation methods for halophilic proteins and large molecular weight complexes
  • Biophysics in extreme conditions : Small-angle scattering (SAXS/SANS). High pressure studies (enzymology, crystallography, spectroscopy). Circular Dichroism.

Major publications

  • Kalimeri M, Girard E, Madern D and Sterpone F.(2014) Interface matters: The stiffness route to stability of a thermophilic tetrameric malate dehydrogenase. Plos One in press
  • Appolaire A, Girard E, Colombo M, Durá MA, Moulin M, Härtlein M, Franzetti B, Gabel F. (2014) Small-angle neutron scattering reveals the assembly mode and oligomeric architecture of TET, a large, dodecameric aminopeptidase. Acta Crystallogr. D70(Pt 11), 2983-2993.
  • Appolaire A, Durá MA, Ferruit M, Andrieu JP, Godfroy A, Gribaldo S, Franzetti B. (2014) The TET2 and TET3 aminopeptidases from Pyrococcus horikoshii form a hetero-subunit peptidasome with enhanced peptide destruction properties. Mol Microbiol. 94(4), 803-814.
  • Lapinaite A, Simon B, Skjaerven L, Rakwalska-Bange M, Gabel F, Carlomagno T. (2013) The structure of the box C/D enzyme reveals regulation of RNA methylation. Nature 502(7472), 519-523.
  • Appolaire, A., Rosenbaum, E., Durá, M.A., Colombo, M., Marty, V., Noirclerc Savoye, M., Godfroy, A., Schoehn, G., Girard, E., Gabel, F. and Franzetti B. (2013) Pyrococcus horikoshii TET2 peptidase assembling process and associated functional regulation. J. Biol. Chem. 288(31), 22542-22554.
  • Fourme R, Girard E, Akasaka K. (2012) High-pressure macromolecular crystallography and NMR: status, achievements and prospects. Curr Opin Struct Biol. 22(5), 636-642.

The list of all the publications of the group is available here.