{PDOC51965}
{PS51965; AG_I_II_AR}
{BEGIN}
**********************************************************************
* 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  alpha-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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: February 2021 / First entry.

[ 1] Demuth D.R., Irvine D.C.
     "Structural and functional variation within the alanine-rich
     repetitive domain of  streptococcal antigen I/II."
     Infect. Immun. 70:6389-6398(2002).
     PubMed=12379719; DOI=10.1128/iai.70.11.6389-6398.2002
[ 2] Brady L.J., Maddocks S.E., Larson M.R., Forsgren N., Persson K.,
     Deivanayagam C.C., Jenkinson H.F.
     "The changing faces of Streptococcus antigen I/II polypeptide family
     adhesins."
     Mol. Microbiol. 77:276-286(2010).
     PubMed=20497507; DOI=10.1111/j.1365-2958.2010.07212.x
[ 3] Manzer H.S., Nobbs A.H., Doran K.S.
     "The Multifaceted Nature of Streptococcal Antigen I/II Proteins in
     Colonization and Disease Pathogenesis."
     Front. Microbiol. 11:602305-602305(2020).
     PubMed=33329493; DOI=10.3389/fmicb.2020.602305
[ 4] Larson M.R., Rajashankar K.R., Patel M.H., Robinette R.A.,
     Crowley P.J., Michalek S., Brady L.J., Deivanayagam C.
     "Elongated fibrillar structure of a streptococcal adhesin assembled by
     the high-affinity association of alpha- and PPII-helices."
     Proc. Natl. Acad. Sci. U. S. A. 107:5983-5988(2010).
     PubMed=20231452; DOI=10.1073/pnas.0912293107

--------------------------------------------------------------------------------
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and
distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives
(CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html
--------------------------------------------------------------------------------

{END}