Lead


Lay summary
The ATP-dependent integral membrane protease FtsH is universally conserved in bacteria. Orthologs exist in chloroplasts and mitochondria, where in humans the loss of a close FtsH-homolog, named paraplegin, causes a form of spastic paraplegia. The first crystal structure of an FtsH construct which is active in ATPase and proteolytic assays has been determined at 2.44 A resolution in our laboratory. It reveals a hexameric molecule built by two stacked rings. One ring contains the proteolytic domains and forms a regular hexagon. The third zinc ligand had been miss-assigned to a glutamic acid before. We identified it correctly as an conserved aspartic acid. This finding classifies FtsH as a novel Asp-zincin. The other ring is formed by the AAA domains, which are all ADP loaded, and shows C2 symmetry only. The symmetry mismatch indicates a model for ATP-driven unfolding and translocation of the substrate polypeptide chain. This model could be largely confirmed by a recent crystal structure determination of a different crystal from at 2.7 A resolution.The carboxy-terminal domain of eukaryotic initiation factor 5 (eIF5) plays a central role in the formation of the multifactor complex (MFC), an important intermediate for the 43 S preinitiation complex assembly. The crystal structure of this domain has been determined by us at 1.8 A resolution. This domain of the protein is exclusively composed out of alpha-helices and is homologous to the carboxy-terminal domain of eIF2B-? (eIF2B?-CTD). Currently we are working on various complexes between different eIFs