Conserved serine and histidine residues are critical for activity of the ER-type signal peptidase SipW of Bacillus subtilis

Type I signal peptidases (SPases) are required for the removal of signal pe ptides from translocated proteins and, subsequently, release of the mature protein from the trans side of the membrane. Interestingly, prokaryotic (P- type) and endoplasmic reticular (ER-type) SPases are functionally equivalen t, but structurally quite different, forming two distinct SPase families th at share only few conserved residues. P-type SPases were, so far, exclusive ly identified in eubacteria and organelles, whereas ER-type SPases were fou nd in the three kingdoms of life. Strikingly, the presence of ER-type SPase s appears to be limited to sporulating Grampositive eubacteria. The present studies were aimed at the identification of potential active site residues of the ER-type SPase SipW of Bacillus subtilis, which is required for proc essing of the spore-associated protein Task Conserved serine, histidine, an d aspartic acid residues are critical for SipW activity, suggesting that th e ER-ty-pe SPases employ a Ser-His-Asp catalytic tried or, alternatively, a Ser-His catalytic dyad. In contrast, the P-type SPases employ a Ser-Lys ca talytic dyed (Paetzel, M., Dalbey, R. E., and Strynadka, N. C. J. (1998) Na ture 396, 186-190). Notably, catalytic activity of SipW was not only essent ial for pre-Task processing, but also for the incorporation of mature Task into spores.