Proteolytic cleavage and cell wall anchoring at the LPXTG motif of surface proteins in Gram‐positive bacteria

Abstract

Many surface proteins are thought to be anchored to the cell wall of Gram-positive bacteria via their C-terminus. Cell wall anchoring requires a specific sorting signal, normally located at the predicted C-terminus of surface proteins. Here we show that when placed into the middle of a polypeptide chain, the sorting signal causes the specific cleavage of the precursor as well as the cell wall anchoring of its N-terminal fragment, while the C-terminal fragment remains within the cytoplasm. N-terminal sequencing of the C-terminal cleavage fragment suggests that the cleavage site is located between threonine (T) and glycine (G) of the LPXTG motif, the signature sequence of cell wall sorting signals. All surface proteins harbouring an LPXTG sequence motif may therefore be cleaved and anchored by a universal mechanism. We also propose a novel hypothesis for the cell wall linkage of surface proteins in Gram-positive bacteria.

A second IgG-binding protein in Staphylococcus aureus

“…1 b, wall-spanning domains. However, in this case the proline-rich region is n o t followed by the cell-wallsorting L P X T G motif (Schneewind et af., 1992(Schneewind et af., , 1995Navarre & Schneewind, 1994 …”

“…We now report on cloning and nucleotide sequence determination of the gene encoding this novel IgG-binding protein. The gene encodes a protein of 436 amino acids with one functional IgG-binding domain and without the typical Gram-positive cell wall anchoring sequence LPXTG (Schneewind et al, 1992(Schneewind et al, , 1995Navarre & Schneewind, 1994), suggesting that the protein is not anchored in the cell wall. This gene is present in all tested strains of S. aureus.…”

EsxA and EsxB are secreted by an ESAT-6-like system that is required for the pathogenesis ofStaphylococcus aureusinfections

“…As a control for polypeptides that are covalently anchored to the cell wall, we also examined staphylococcal protein A (27). Cell wall degradation products, i.e., peptidoglycan fragments with linked polypeptide, are being released from the staphylococcal surface, and some protein A can therefore be found in both the total lysate and culture medium (28) (Fig. 2 A).…”

An iron-regulated sortase anchors a class of surface protein during Staphylococcus aureus pathogenesis

“…Surface proteins play important roles in the pathogenesis of Gram-positive bacterial infections (7) and are anchored to the cell wall by a mechanism requiring a C-terminal sorting signal (8). Sorting signals are composed of an LPXTG motif, a hydrophobic domain, and a tail of positively charged residues (9,10).…”