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 D (4) symmetry and referred to as CubicO. We solved the structure of the Pyrococcus abyssi Pab87 protein at 2.2 Å resolution using the anomalous signal of the high-phasing-power lanthanide derivative Lu-HPDO3A. A 20 Å wide channel runs through this supramolecular assembly of 0.4 MDa, giving access to a 60 Å 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.