x-ray-crystallography-to-study-oligomeric-state-transition-thermotoga

X-Ray Crystallography to Study the Oligomeric State Transition of the <em>Thermotoga maritima</em> M42 Aminopeptidase TmPep1050

The M42 aminopeptidases form functionally active complexes made of 12 subunits. Their assembly process appears to be regulated by their metal ion ...

Labiris Institut de Recherche

The M42 aminopeptidases are dinuclear aminopeptidases displaying a peculiar tetrahedron-shaped structure with 12 subunits. Their quaternary structure results from the self-assembly of six dimers controlled by their divalent metal ion cofactors. The oligomeric-state transition remains debated despite the structural characterization of several archaeal M42 aminopeptidases. The main bottleneck is the lack of dimer structures, hindering the understanding of structural changes occurring during the oligomerization process. We present the first dimer structure of an M42 aminopeptidase, TmPep1050 of , along with the dodecamer structure. The comparison of both structures has allowed us to describe how the metal ion cofactors modulate the active-site fold and, subsequently, affect the interaction interface between dimers. A mutational study shows that the M1 site strictly controls dodecamer formation. The dodecamer structure of TmPep1050 also reveals that a part of the dimerization domain delimits the catalytic pocket and could participate in substrate binding.

Nathalie Brandt

Labiris Institut de Recherche

X-Ray Crystallography to Study the Oligomeric State Transition of the Thermotoga maritima M42 Aminopeptidase TmPep1050