Ectodomains 3 and 4 of human polymeric Immunoglobulin receptor (hpIgR) mediate invasion of Streptococcus pneumoniae into the epithelium.
Streptococcus pneumoniae binds to the ectodomain of the human polymeric Ig receptor (pIgR), also known as secretory component (SC), via a hexapeptide motif in the choline-binding protein SpsA. The SpsA-pIgR interaction mediates adherence and internalization of the human pathogen into epithelial cells. In this study the results of SpsA binding to human, mouse, and chimeric SC strongly supported the human specificity of this unique interaction and suggested that binding sites in the third and fourth Ig-like domain of human SC (D3 and D4, respectively) are involved in SpsA-pIgR complex formation. Binding of SpsA to SC-derived synthetic peptides indicated surface-located potential binding motifs in D3 and D4. Adherence and uptake of pneumococci or SpsA-coated latex beads depended on the SpsA hexapeptide motif as well as SpsA-binding sites in D3 and D4 of human pIgR. The involvement of D3 and D4 in adherence and invasion was demonstrated by the lack of binding of SpsA-coated latex beads to transfected epithelial cells expressing mutated pIgR. Finally, blocking experiments with chimeric human-mouse SC as well as synthetic peptides indicated the participation of D3 and a key role of D4 in pneumococcal invasion.
Elm
Christine
C
GBF-German Research Centre for Biotechnology, Braunschweig 38124, Germany.
Braathen
Ranveig
R
Bergmann
Simone
S
Frank
Ronald
R
Vaerman
Jean-Pierre
JP
Kaetzel
Charlotte S
CS
Chhatwal
Gursharan S
GS
Johansen
Finn-Eirik
FE
Hammerschmidt
Sven
S
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000737:chemistry; D001665:Binding Sites; D002460:Cell Line; D002794:Choline / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D004285:Dogs; D000939:Epitopes; D004926:Escherichia coli / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D007700:Kinetics; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013296:Streptococcus pneumoniae / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D013997:Time Factors; D014162:Transfection
D001426:Bacterial Proteins; D018076:DNA, Complementary; D000939:Epitopes; D010455:Peptides; D011993:Recombinant Fusion Proteins; C110344:SpsA protein, Streptococcus pneumoniae; D002794:Choline