Crystal structure of Bacillus subtilis CodW, a noncanonical HslV-like peptidase with an impaired catalytic apparatus.

摘要

ATP-dependent proteases play vital roles in protein quality control and in regulating the levels of certain cellular proteins.Escherichia coli and other bacteria, including Bacillus subtilis, contain at least three types of multi-meric ATP-dependent proteases homologous to the eu-karyotic 26S proteasome: Lon, Clp and HslVU. Of these, HslVXJ has been extensively studied as the simplest proteasome ancestor. Like the 26S proteasome, HslVU is comprised of two multimeric components: the ATPase HslU, which belongs to the AAA superfamily of ATPases, and the peptidase HslV, which shares common structural features with the catalytic beta-type subunits of the 20S proteasome. Despite a sequence identity of only about 20%, they share the amino acids crucial for proteol-ysis and auto-cleavage [Fig. 1(A)]. Moreover, both use a threonine residue at the N-terminus as a catalytic nucleo-phile exposed by the processing of a methionine residue or a prosegment upon assembly, and are thus members of the N-terminal nucleophile (Ntn)-hydrolase family.