Structural basis of highly conserved ribosome recycling in eukaryotes and archaea

Ribosome-driven protein biosynthesis is comprised of four phases: initiation, elongation, termination and recycling. In bacteria, ribosome recycling requires ribosome recycling factor and elongation factor G, and several structures of bacterial recycling complexes have been determined. In the eukaryotic and archaeal kingdoms, however, recycling involves the ABC-type ATPase ABCE1 and little is known about its structural basis. Here we present cryo-electron microscopy reconstructions of eukaryotic and archaeal ribosome recycling complexes containing ABCE1 and the termination factor paralogue Pelota. These structures reveal the overall binding mode of ABCE1 to be similar to canonical translation factors. Moreover, the iron-sulphur cluster domain of ABCE1 interacts with and stabilizes Pelota in a conformation that reaches towards the peptidyl transferase centre, thus explaining how ABCE1 may stimulate peptide-release activity of canonical termination factors. Using the mechanochemical properties of ABCE1, a conserved mechanism in archaea and eukaryotes is suggested that couples translation termination to recycling, and eventually to re-initiation.     

Collagenolytic enzymes in human serum

Zusammenfassung Mit Hilfe des synthetischen Kollagenasesubstrates PZ-Pro-Leu-Gly-Pro-D-Arg wurden im humanen Serum kollagenolytische Enzyme nachgewiesen, deren Spezifität der Clostridiopeptidase A entspricht. Die Spaltungsgeschwindikeit zeigt in Abhängigkeit von pH ein Optimum bei pH 7,2 und bei pH 8,0. Das spricht für die Existenz zweier Enzyme. Zur quantitativen Bestimmung der Enzymaktivitäten wurde eine Methode ausgearbeitet, mit der eine Reihe von normalen humanen Seren analysiert wurde.     

Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer

PALB2 was recently identified as a nuclear binding partner of BRCA2. Biallelic BRCA2 mutations cause Fanconi anemia subtype FA-D1 and predispose to childhood malignancies. We identified pathogenic mutations in PALB2 (also known as FANCN) in seven families affected with Fanconi anemia and cancer in early childhood, demonstrating that biallelic PALB2 mutations cause a new subtype of Fanconi anemia, FA-N, and, similar to biallelic BRCA2 mutations, confer a high risk of childhood cancer.