Signal peptidase I: Cleaving the way to mature proteins

Abstract

Signal peptidase I (SPase I) is critical for the release of translocated preproteins from the membrane as they are transported from a cytoplasmic site of synthesis to extracytoplasmic locations. These proteins are synthesized with an amino-terminal extension, the signal sequence, which directs the preprotein to the Sec-or Tat-translocation pathway. Recent evidence indicates that the SPase I cleaves preproteins as they emerge from either pathway, though the steps involved are unclear. Now that the structure of many translocation pathway components has been elucidated, it is critical to determine how these components work in concert to support protein translocation and cleavage. Molecular modeling and NMR studies have provided insight on how the preprotein docks on SPase I in preparation for cleavage. This is a key area for future work since SPase I enzymes in a variety of species have now been identified and the inhibition of these enzymes by antibiotics is being pursued. The eubacterial SPase I is essential for cell viability and belongs to a unique group of serine endoproteases which utilize a Ser-Lys catalytic dyad instead of the prototypical Ser-His-Asp triad used by eukaryotes. As such, SPase I is a desirable antimicrobial target. Advances in our understanding of how the preprotein interfaces with SPase I during the final stages of translocation will facilitate future development of inhibitors that display a high efficacy against SPase I function.

A Type I Signal Peptidase Is Required for Pilus Assembly in the Gram-Positive, Biofilm-Forming Bacterium Actinomyces oris

“…GspA is 1 of 18 cell wall-anchored proteins with a CWSS and a putative signal peptide. A typical signal peptide is composed of a net positively charged (n) region, followed by a hydrophobic (h) region and a cleavage (c) region (25) (Fig. 4A).…”

“…4A). The c region harbors a typical cleavage site, i.e., an AXA motif, that is recognized and cleaved by a type I SPase after the second Ala residue (25). To determine the cleavage site of GspA and the roles of LepB1 and LepB2 in this process, we purified GspA by affinity chromatography from A. oris strains lacking either gene or both and analyzed the N termini of the purified proteins by Edman degradation.…”

Deletion of Synechocystis sp. PCC 6803 Leader Peptidase LepB1 Affects Photosynthetic Complexes and Respiration

“…In contrast to other Gram-negative bacteria, almost all the cyanobacterial genomes analyzed so far contain two lep genes. Although the overall sequence identity of leader peptidases from various species is relatively low, five conserved regions were identified in the catalytic domain, called boxes B, C, D, and E, as well as the membrane anchor domain A (22,23). Both LepB1 and LepB2 in Synechocystis have the conserved A-E boxes (21,23), including the invariant amino acid residues demonstrated to be essential for catalytic activity.…”

Extracellular gluco-oligosaccharide degradation by Caulobacter crescentus

“…Additional database analyses (LipoP1.0/SignalP 4.1 servers) for signal sequences revealed all three putative membrane-associated proteins: CC_1756, CC_1757, CC_2227 (Table 1) possess a signal peptidase I (SPase I) cleavage site, indicating their subcellular localization is beyond the inner membrane, i.e. periplasm and/or outer membrane (Auclair et al, 2012;Juncker et al, 2003). Dodd et al (2011) proposed a model for xylan degradation by rumen and human colonic bacterioides involving outer membrane-bound extracellular xylanase that possesses an SPase II cleavage site; however, the mechanism of protein localization on the outer leaflet of the outer membrane remains unknown (Tokuda, 2009).…”