Epithelial mucins and bacterial adhesion - Carbohydrate Chemistry: Chemical and Biological Approaches - page 615

Lys/Arg
patches

MIDAS
trench

D3

D2

D1

D4

Fig. 6 The RrgA adhesin from Streptococcus pneumoniae, showing the overall struc-
ture, the conserved MIDAS motif and the arms extending from the D3 domain that contain
streptococcal species and strain-variable positive charges. 119

pilin protein RrgB together with an adhesin, RrgA. The 1.90 Å-resolution
crystal structure of the 893-residue elongated RrgA shows four domains,
with in the most external D3 domain a MIDAS trench. 119 The MIDAS
region (metal-ion-dependent adhesion site) is similar to what is known
for eukaryotic proteins, such as integrins, that are known to bind to
extracellular matrix proteins. Beyond the MIDAS motif, the D3 domain
extends outwards with two highly positively charged arms (Fig. 6). In
contrast to the constellation of residues stabilizing the MIDAS motif that
is highly conserved among streptococcal spp., notable variation of the
multiple lysine and also arginine residues in the arms are obvious with
other species (S. agalactiae and S. pyogenes). Species- and strain-
dependent variations could modulate interactions with host receptor
molecules that on their turn could also be charge-differentiated for in-
stance by reversibly modifying their glycans with negatively charged sialic
acids or sulfate groups.

6 Conclusion
During the last decades, many efforts have been made to determine the
structure and the heterogeneity of mucin-type O-glycans, showing the
presence of a large number of terminal antigens that serve as counter
receptors for bacteria. Alterations in mucin-type O-Glycosylation have
been observed in different pathologies and correlated with chronic in-
fection of gastrointestinal tract and airway. At the present time, the
regulation of mucin O-glycans chains as well as the mechanisms by
which the glycosylation is modified in pathological conditions remain