The Human Polymeric Immunoglobulin Receptor Binds to Streptococcus pneumoniae via Domains 3 and 4

Ling Lu, Michael E. Lamm, Hongmin Li, Blaise Corthesy, Jing Ren Zhang

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Streptococcus pneumoniae (the pneumococcus) is a major cause of bacterial pneumonia, middle ear infection (otitis media), sepsis, and meningitis. Our previous study demonstrated that the choline-binding protein A (CbpA) of S. pneumoniae binds to the human polymeric immunoglobulin receptor (pIgR) and enhances pneumococcal adhesion to and invasion of cultured epithelial cells. In this study, we sought to determine the CbpA-binding motif on pIgR by deletional analysis. The extracellular portion of pIgR consists of five Ig-like domains (D1-D5), each of which contains 104-114 amino acids and two disulfide bonds. Deletional analysis of human pIgR revealed that the lack of either D3 or D4 resulted in the loss of CbpA binding, whereas complete deletions of domains D1, D2, and D5 had undetectable impacts. Subsequent analysis showed that domains D3 and D4 together were necessary and sufficient for the ligand-binding activity. Furthermore, CbpA binding of pIgR did not appear to require Ca2+ or Mg2+. Finally, treating pIgR with a reducing agent abolished CbpA binding, suggesting that disulfide bonding is required for the formation of CbpA-binding motif(s). These results strongly suggest a conformational CbpA-binding motif(s) in the D3/D4 region of human pIgR, which is functionally separated from the IgA-binding site(s).

Original languageEnglish (US)
Pages (from-to)48178-48187
Number of pages10
JournalJournal of Biological Chemistry
Volume278
Issue number48
DOIs
StatePublished - Nov 28 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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