Structure of the Archaeal Pab87 Peptidase Reveals a Novel Self-Compartmentalizing Protease Family

Self-compartmentalizing proteases orchestrate protein turnover through an original architecture characterized by a central catalytic chamber. Here we report the first structure of an archaeal member of a new self-compartmentalizing protease family forming a cubic-shaped octamer with D4 symmetry and referred to as CubicO. We solved the structure of the Pyrococcus abyssi Pab87 protein at 2.2 angstrom resolution using the anomalous signal of the high-phasing-power lanthanide derivative Lu-HPDO3A. A 20 angstrom wide channel runs through this supramolecular assembly of 0.4 MDa, giving access to a 60 angstrom wide central chamber holding the eight active sites. Surprisingly, activity assays revealed that Pab87 degrades specifically D-amino acid containing peptides, which have never been observed in archaea. Genomic context of the Pab87 gene showed that it is surrounded by genes involved in the amino acid/peptide transport or metabolism. We propose that CubicO proteases are involved in the processing of D-peptides from environmental origins.