PROSITE documentation PDOC00373 [for PROSITE entry PS50847]

Gram-positive cocci surface proteins LPxTG motif profile

Surface proteins from Gram-positive cocci are covalently linked to the bacterial cell wall by sortase, a membrane-anchored transpeptidase that cleaves proteins between the threonine and the glycine of a conserved LPxTG motif, with the formation of a thioester between the conserved cysteine of sortase and the threonine carboxyl group. The newly liberated C-terminus of the threonine is transferred via an amide bond exchange to the amino group of the pentaglycine wall crossbridge, thereby tethering the C-terminus end of the surface protein to the bacterial peptidoglycan [1,2,3].

Surface proteins from Gram-positive cocci contain an N-terminal signal peptide and a C-terminal sorting signal. The 35-residue sorting signal is composed of a conserved LPxTG motif, a hydrophobic domain, and a tail of positively charged residues. This structure is represented in the following schematic representation:

                                           +-- sorting signal ---+
                                           |                     |
  +------+---------------------------------+-----+-------------+-+
  |Signal|                                 |LPxTG| Hydrophobic |+|
  +------+---------------------------------+-----+-------------+-+

  'Signal': signal peptide;
  'Hydrophobic': hydrophobic domain;
  '+': positive charged tail.

In the case of immunoglobulin A1 proteases, the typical gram-positive cell wall anchor motif LPxTG is located in their N-terminal regions, in contrast with other known streptococcal and staphylococcal proteins [4].

Some proteins known to contain LPxTG motif containing sorting signal are listed below:

• Aggregation substance from streptococcus faecalis (asa1).
• C5a peptidase from Streptococcus pyogenes (scpA).
• C protein α-antigen from Streptococcus agalactiae (bca).
• Cell surface antigen I/II (PAC) from Streptococcus mutans.
• Dextranase from Streptococcus downei (dex).
• Fibronectin-binding protein from Staphylococcus aureus (fnbA).
• Fimbrial subunits from Actinomyces naeslundii and viscosus.
• IgA binding protein from Streptococcus pyogenes (arp4).
• IgA binding protein (B antigen) from Streptococcus agalactiae (bag).
• IgG binding proteins from Streptococci and Staphylococcus aureus.
• Internalin A from Listeria monocytogenes (inlA).
• M proteins from streptococci.
• Muramidase-released protein from Streptococcus suis (mrp).
• Nisin leader peptide processing protease from Lactococcus lactis (nisP).
• Protein A from Staphylococcus aureus.
• Trypsin-resistant surface T protein from streptococci.
• Wall-associated protein from Streptococcus mutans (wapA).
• Wall-associated serine proteinases from Lactococcus lactis.

The profile we developed covers the LPxTG motif, the hydrophobic stretch and the positively charged region.