Proteasome interaction network in archaea

Principal Investigator: Bruno Franzetti

Group members involved: Eric Girard, Frank Gabel, Jacques Covès, Mylène Ferruit

In all cell types the proteasome system is responsible for the efficient destruction of damaged cellular components in stress conditions. This activity is essential for extremophilic adaptation. Understanding how the proteasomes select disabled molecular edifices represent a major challenge in fundamental and biomedical research. Archaea possess eukaryotic-like proteasomes and ubiquitin-like protein modifications systems. In collaboration with the Group of J. Maupin Furlow (Univ Florida), we solved the structure of an archaeal deubiquitinase in complex with the archaeal ubiquitin-like molecule. Recently, using pull down and genetic approaches in collaboration with our partners at LM2E we identified unexpected proteasome interactants indicating the existence of a novel quality control and surveillance pathway in thermococcales. In a new project we are developing novel approaches to unravel the structures and mode of action of the core components of this network. For this, we use in vitro interaction and biochemical assays combined with the structural studies of native holo-complexes purified from archaea using cutting-edge X-ray crystallography tools developed in the group and CryoEM (collaboration with G. Schoehn- EM group IBS).

Figure 1: Structure of an archaeal JAMM-like deubiquitinase in complex with an archaeal ubiquitin-like protein modifier (SAMP). Cao et al. (2017) Structure.


  • ANR project “Prote-IN”. 2019-2022. ANR-18-CE11-0018-01 


Selected publications:

  • Structural Insight into Ubiquitin-Like Protein Recognition and Oligomeric States of JAMM/MPN(+) Proteases. Shiyun Cao, Sylvain Engilberge, Eric Girard, Frank Gabel, Bruno Franzetti, Julie A Maupin-Furlow. Structure, 2017.
  • Stress regulation of the PAN-proteasome system in the extreme halophilic archaeon Halobacterium. Chamieh H, Marty V, Guetta D, Perollier A and Franzetti B. Extremophiles (2012) 16(2) : 215-225.
  • The two PAN ATPases from Halobacterium display N-terminal heterogeneity and form labile complexes with the 20S proteasome. Chamieh H, Guetta D and Franzetti B. Biochemical Journal (2008) 411(2) : 387-397