title: Signal peptidase I processed secretory signal sequences: Selection for and against specific amino acids at the second position of mature protein.
abstract: Signal peptides direct proteins from the cytoplasm to the periplasm. These N-terminal peptides are cleaved upon entry to the periplasm by either signal peptidase I, or signal peptidase II for lipoproteins. Signal peptidase I is a serine protease that has either a serine-lysine or serine-histidine catalytic dyad present in the active site. The recognition site for signal peptide cleavage by signal peptidase I has been defined primarily by an Ala-X-Ala motif at the C-terminal end of the signal peptide, one amino acid away from the cleavage site. We used a verified set of signal peptidase I cleaved proteins from E. coli to look for novel conserved features, focusing on the N-terminus of the mature protein. We observed a striking bias for the presence of acidic residues at second position of the mature protein (P2'), and a complete absence of aromatic amino acids at the same position. Whole genome analysis of the predicted set of all E. coli and B. subtilis secreted proteins confirmed the same strong bias for acidic residues at P2' of the mature protein, and against aromatic amino acids at the same position. When these studies were extended to archaeal genomes (M. voltae and S. tokodaii) and the yeast genome from S. cerevisiae, this bias was not observed. E. coli and B. subtilis primarily express a signal peptidase I contains a serine-lysine catalytic dyad, whilst those of archaeal and eukaryotic origin generally have a serine-histidine catalytic dyad. This difference may explain the differential bias for acidic residues and against aromatic residues at P2'. These observations suggest additional key residues that may favor or prevent signal sequence recognition or cleavage by signal peptidase I, and thereby facilitate more accurate in silico prediction of signal peptidase I cleavage sites.
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast Campus, Gold Coast, Qld 4222, Australia.
authors.forename: Yaramah M
authors.initials: YM
authors.lastname: Zalucki
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast Campus, Gold Coast, Qld 4222, Australia. Electronic address: m.jennings@griffith.edu.au.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Jennings
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001412:Bacillus subtilis / Q000201:enzymology / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020134:Catalytic Domain / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D019843:Archaeal Proteins; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D021382:Protein Sorting Signals; D029701:Saccharomyces cerevisiae Proteins; D012697:Serine Endopeptidases; C026515:type I signal peptidase
keywords: Amino acid bias; Cleavage site; Secretion; Signal peptidase I; Signal peptide