Inactive dimeric structure of the protease domain of stomatin operon partner protein

The N‐terminal region of the stomatin operon partner protein (STOPP) PH1510 (1510‐N) from the hyperthermophilic archaeon Pyrococcus horikoshii is a serine protease with a catalytic Ser–Lys dyad (Ser97 and Lys138) and specifically cleaves the C‐terminal hydrophobic region of the p‐stomatin PH1511. In a form of human hemolytic anemia known as hereditary stomatocytosis, stomatin is deficient in the erythrocyte membrane owing to mis‐trafficking. Stomatin is thought to act as an oligomeric scaffolding protein to support cell membranes. The cleavage of stomatin by STOPP might be involved in a regulatory system. Several crystal structures of 1510‐N have previously been determined: the wild type, the K138A mutant and its complex with a substrate peptide. Here, the crystal structure of the S97A mutant of 1510‐N (1510‐N S97A) was determined at 2.25 Å resolution. The structure contained two 1510‐N S97A molecules in the asymmetric unit. On the superposition of one monomer of the 1510‐N S97A and wild‐type dimers, the S97A Cα atom of the other monomer of 1510‐N S97A deviated by 23 Å from that of the wild type. This result indicates that 1510‐N can greatly change the form of its dimer. Because of crystallographic symmetry in space group P65, a sixfold helical structure is constructed using the 1510‐N dimer as a basic unit. This helical structure may be common to STOPP structures. Based on the structure of the N‐terminal region of the S97A mutant of the stomatin operon partner protein PH1510 (1510‐N), it was found that the dimeric form differs greatly from those determined previously. This result indicates that 1510‐N can greatly change the form of its dimer.