PROSITE documentation PDOC51965

Streptococcus antigen I/II alanine-rich (Ag I/II A) repeat profile

The genus Streptococcus is a heterogeneous group of Gram-positive bacteria that can be part of the natural microbiota. Various streptococci are commonly isolated from the oral cavity, intestines, or female reproductive tracts in healthy humans. These colonizing streptococci are often commensal organisms that persist without causing disease. In some cases, colonization by commensal streptococci can actually benefit the host through mechanisms such as niche competition or direct inhibition of more pathogenic organisms; however, there are also many streptococcal species that are opportunistic pathogens with the potential to cause severe invasive disease. Antigen I/II (Ag I/II) family proteins are sortase anchored cell surface adhesins that are nearly ubiquitous across streptococci and contribute to many streptococcal diseases, including dental caries, respiratory tract infections, and meningitis. They appear to be multifunctional adhesins with affinities to various host substrata, acting to mediate attachment to host surfaces and stimulate immune responses from the colonized host. Each of the polypeptides possesses seven structural regions, comprising a signal sequence, a highly charged N-terminal region, an alanine-rich repetitive domain (A region), a globular domain termed the V-domain based on the variability observed in this region between strains, a proline-rich repetitive region (P region), a C-terminal domain, and cell wall-anchoring sequences (see <PDOC00373>). The A region typically consists of 3-4 alanine-rich repeats (82 residues each) with 23-30% alanine content. The P region has 3-4 proline-rich repeats (39 residues each) with 35% proline content. The Ag I/II proteins adopt a cell wall-anchored stalk structure formed by interactions between the intertwined A- and P-domains, which projects the V-domain containing a binding cleft away from the cell surface. This cleft may be used to promote streptococcal colonization of various tissues via both direct cellular adherence or interaction with extracellular matrix components [1,2,3,4].

The A region exhibits a seven residue periodicity of hydrophobic amino acids, suggesting that it may form a coiled coil. The Streptococcus Ag I/II A repeat forms a long α-helix that intimately intertwines into a left-handed supercoiled structure with the P repeat polyproline II (PPII) helix to form an unusually long and narrow stalk (see <PDB:3IPK>) [4].

The profile we developed covers the entire Streptococcus Ag I/II A repeat.