The group B streptococcal alpha C protein binds alpha1beta1-integrin through a novel KTD motif that promotes internalization of GBS within human epithelial cells.
Group B Streptococcus (GBS) is the leading cause of bacterial pneumonia, sepsis and meningitis among neonates and a cause of morbidity among pregnant women and immunocompromised adults. GBS epithelial cell invasion is associated with expression of alpha C protein (ACP). Loss of ACP expression results in a decrease in GBS internalization and translocation across human cervical epithelial cells (ME180). Soluble ACP and its 170 amino acid N-terminal region (NtACP), but not the repeat protein RR', bind to ME180 cells and reduce internalization of wild-type GBS to levels obtained with an ACP-deficient isogenic mutant. In the current study, ACP colocalized with alpha(1)beta(1)-integrin, resulting in integrin clustering as determined by laser scanning confocal microscopy. NtACP contains two structural domains, D1 and D2. D1 is structurally similar to fibronectin's integrin-binding region (FnIII10). D1's (KT)D146 motif is structurally similar to the FnIII10 (RG)D1495 integrin-binding motif, suggesting that ACP binds alpha(1)beta(1)-integrin via the D1 domain. The (KT)D146A mutation within soluble NtACP reduced its ability to bind alpha(1)beta(1)-integrin and inhibit GBS internalization within ME180 cells. Thus ACP binding to human epithelial cell integrins appears to contribute to GBS internalization within epithelial cells.
Bolduc
Gilles R
GR
Department of Medicine, Brigham and Women's Hospital, 75 Fransis Street, Boston, MA 02115, USA.|Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115, USA.
Madoff
Lawrence C
LC
Department of Medicine, Brigham and Women's Hospital, 75 Fransis Street, Boston, MA 02115, USA.|Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115, USA.
D020816:Amino Acid Motifs; D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018988:Bacterial Translocation; D001665:Binding Sites; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology*; D006801:Humans; D039222:Integrin alpha1beta1 / Q000378:metabolism*; D018613:Microscopy, Confocal; D008958:Models, Molecular; D011485:Protein Binding; D013292:Streptococcus agalactiae / Q000472:pathogenicity*
D000954:Antigens, Surface; D001426:Bacterial Proteins; D039222:Integrin alpha1beta1; C077961:alpha C protein, group B streptococci