beta-Propeller repeats and a PDZ domain in the tricorn protease: predictedself-compartmentalisation and C-terminal polypeptide-binding strategies ofsubstrate selection

Prokaryotic proteases demonstrate a variety of substrate-selection strategi es that prevent uncontrolled protein degradation. Proteasomes and ClpXP-lik e proteases form oligomeric structures that exclude large substrates from c entral solvated chambers containing their active sites. Monomeric prolyl ol igopeptidases have been shown to contain beta-propeller structures that sim ilarly reduce access to their catalytic residues. By contrast, Tsp-like enz ymes contain PDZ domains that are thought to specifically target C-terminal polypeptides. We have investigated the sequence of Thermoplasma acidophilu m? I tricorn protease using recently-developed database search methods. The tricorn protease is known to associate into a 20 hexamer capsid enclosing an extremely large cavity that is 37 nm in diameter. II is unknown, however , how this enzyme selects its small oligopeptide substrates. Our results de monstrate the presence in tricorn protease of a PDZ domain and two predicte d six-bladed beta-propeller domains. We suggest that the PDZ domain is invo lved in targeting non-polar C-terminal peptides, similar to those generated by the T. acidophilum proteasome, whereas the beta-propeller domains serve to exclude large substrates from the tricorn protease active site in a sim ilar manner to that previously indicated for prolyl oligopeptidase. (C) 199 9 Federation of European Microbiological Societies. Published by Elsevier S cience B.V. All rights reserved.