Figure 1

(A): Classification of protein SCLs in Gram-positive bacteria. The secreted proteins can be divided into the following subgroups: (i) N-terminal hydrophobic tail anchored (N-anchored), (ii) C-terminal hydrophobic tail anchored (C-anchored), (iii) covalent lipid-anchored, (iv) covalently/non-covalently cell-wall anchored, (v) secreted/released (defined as proteins that are Sec-/Tat-secreted and cleaved by the signal peptidase I), and (vi) non-classically secreted/released proteins via minor pathways [120, 163]. Based on the Swiss Prot classification system the SCLs could be categorized into: Cytoplasmic, Membrane (multi-transmembrane, N-/C-anchored), Cell wall (LPxTG-anchored) and Extracellular (lipid-anchored, secreted, bacteriocin-like) proteins. (B): The structure of known signal peptides. The overall structure of Tat- and Sec-dependent signal peptides is commonly conserved as distinct consecutive N, H and C regions. The N region is the start of the protein containing positively charged residues. The H region follows the N region and is a string of consecutive hydrophobic residues which can form an α-helix in the membrane. The C region contains the signal peptidase cleavage signals. Known cleavage/retention signals include the AxAA type I SPase cleavage site [163, 172], the L-x-x-C (so-called lipobox) type II SPase cleavage site [157] and the AxA Tat-substrate cleavage site [88, 90, 173]. The LPxTG-type motif is a C-terminal sorting signal which is involved in the covalent attachment of proteins to the peptidoglycan of the cell wall. The signal peptide of proteins targeted for minor secretion pathways does not follow the N-H-C structure [2, 125, 163].