LPXTG

LPXTG is a conserved cell wall sorting signal found in many Gram-positive bacteria. The motif consists of the amino acid sequence Leu-Pro-X-Thr-Gly, where X is any amino acid, located near the C-terminus of many surface-exposed proteins that are secreted by the Sec pathway. These proteins typically have an N-terminal signal peptide followed by a cell-wall–anchoring region that includes the LPXTG motif, a hydrophobic transmembrane segment, and a short positively charged tail.

After secretion, sortase enzymes—most notably sortase A—recognize LPXTG and cleave between the threonine and glycine. The enzyme then covalently links the protein to the peptidoglycan of the cell wall, anchoring it outside the cytoplasmic membrane. This covalent attachment enables the displayed proteins to function as adhesins, enzymes, or virulence factors that interact with the host.

LPXTG-anchored proteins play roles in virulence and host interaction in several pathogens, including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, and Listeria monocytogenes. The motif is also a key tool in biotechnology, where sortase-mediated ligation enables covalent attachment of peptides or proteins to LPXTG-bearing anchors for surface display or the construction of protein conjugates.

Variations exist in the surrounding sequence and in the exact context of the sorting signal across species. The LPXTG system continues to be a focal point of study for understanding Gram-positive cell wall assembly and for developing applications in protein engineering.