TET peptidase assembling and mode of action

Principal Investigator: Bruno Franzetti

Group members involved: Eric Girard, Frank Gabel

A large part of archaeal genomes encodes for unknown proteins, many of them being assigned as putative peptidases. We have undertaken the characterization of these orphans proteins with a focus on those forming large oligomeric complexes. Our goal is to specify the link between proteolysis and environmental adaptation and to discover novel cellular functions. The TET peptidases were discovered in the group using native purification of stress-induced proteins in Archaea. TETs represent a novel family of self-compartmentalized proteases comprising 12 subunits forming a unique tetrahedral edifice. TET edifices are conserved in all cell types and exists in several version in hyperthermophilic archaea. We are combining microbiology, enzymology, SAXS-SANS, X-ray crystallography and Cryo-EM to elucidate the physiological role, assembly processes, substrate specificity and basic modes of action of TET peptidases machines.

Figure 1: Non-random assembling sequence of the TET system determined using integrated structural biology study (X-ray crystallography, EM; SAXS/SANS, AUC and enzymology). (Appolaire et al. 2013; Appolaire et al 2014)


  • ANR “Archelyse” 2012-2015 (ANR-12-BSV8-0019-0)
  • LABEX-GRAL “valorisation” program ANR-368 10-LABX-49-01
  • SATT-LINKSIUM Maturation Program

Selected Publications:

  • Characterization of a Glycyl-Specific TET Aminopeptidase Complex from Pyrococcus horikoshii. Hind Basbous, Alexandre Appolaire, Eric Girard, Bruno Franzetti. Journal of Bacteriology, 2018, 200 (17)
  • Tuned by metals: the TET peptidase activity is controlled by 3 metal binding sites. Matteo Colombo, Eric Girard, Bruno Franzetti. Scientific Reports, 2016, 6.
  • Pyrococcus horikoshii TET2 peptidase assembling process and associated functional regulation. Appolaire A, Rosenbaum E, Dura MA, Colombo M, Marty V, Noirclerc Savoye M, Godfroy A, Schoehn G, Girard E, Gabel F and Franzetti B. Journal of Biological Chemistry (2013) 288(31) : 22542-22554
  • Small angle neutron scattering reveals the assembling mode and oligomeric architecture of TET, a large, dodecameric aminopeptidase. Appolaire A, Girard E, Colombo M, Durá MA, Moulin M, Härtlein M, Franzetti B and Gabel F. Acta Crystallogr D Biol Crystallogr. D70 (2014) doi:10.1107/S1399004714018446