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Human Siglec-5 Inhibitory Receptor and Immunoglobulin A (IgA) Have Separate Binding Sites in Streptococcal {beta} Protein.

På svenska

Author

  • Therése Nordström
  • Elin Movert
  • Anders Olin
  • Syed R Ali
  • Victor Nizet
  • Ajit Varki
  • Thomas Areschoug

Summary, in English

Sialic acid-binding immunoglobulin-like lectins (Siglecs) are receptors believed to be important for regulation of cellular activation and inflammation. Several pathogenic microbes bind specific Siglecs via sialic acid-containing structures at the microbial surface, interactions that may result in modulation of host responses. Recently, it was shown that the group B Streptococcus (GBS) binds to human Siglec-5 (hSiglec-5), an inhibitory receptor expressed on macrophages and neutrophils, via the IgA-binding surface β protein, providing the first example of a protein/protein interaction between a pathogenic microbe and a Siglec. Here we show that the hSiglec-5-binding part of β resides in the N-terminal half of the protein, which also harbors the previously determined IgA-binding region. We constructed bacterial mutants expressing variants of the β protein with non-overlapping deletions in the N-terminal half of the protein. Using these mutants and recombinant β fragments, we showed that the hSiglec-5-binding site is located in the most N-terminal part of β (B6N region; amino acids 1-152) and that the hSiglec-5- and IgA-binding domains in β are completely separate. We showed with BIAcore(TM) analysis that tandem variants of the hSiglec-5- and IgA-binding domains bind to their respective ligands with high affinity. Finally, we showed that the B6N region, but not the IgA-binding region of β, triggers recruitment of the tyrosine phosphatase SHP-2 to hSiglec-5 in U937 monocytes. Taken together, we have identified and isolated the first microbial non-sialic acid Siglec-binding region that can be used as a tool in studies of the β/hSiglec-5 interaction.

Publishing year

2011

Language

English

Pages

33981-33991

Publication/Series

Journal of Biological Chemistry

Volume

286

Issue

39

Document type

Journal article

Publisher

American Society for Biochemistry and Molecular Biology

Topic

  • Infectious Medicine
  • Microbiology in the medical area

Status

Published

ISBN/ISSN/Other

  • ISSN: 1083-351X