Human Siglec-5 Inhibitory Receptor and Immunoglobulin A (IgA) Have Separate Binding Sites in Streptococcal {beta} Protein.
(2011) In Journal of Biological Chemistry 286(39). p.33981-33991- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2168572
- author
- Nordström, Therése LU ; Movert, Elin LU ; Olin, Anders LU ; Ali, Syed R ; Nizet, Victor ; Varki, Ajit and Areschoug, Thomas LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 286
- issue
- 39
- pages
- 33981 - 33991
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000295159200030
- pmid:21795693
- scopus:80053206438
- pmid:21795693
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M111.251728
- language
- English
- LU publication?
- yes
- id
- 090925b4-6cca-4183-b666-3fa7ea56da6c (old id 2168572)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21795693?dopt=Abstract
- date added to LUP
- 2016-04-01 10:44:08
- date last changed
- 2022-04-20 05:46:18
@article{090925b4-6cca-4183-b666-3fa7ea56da6c,
abstract = {{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.}},
author = {{Nordström, Therése and Movert, Elin and Olin, Anders and Ali, Syed R and Nizet, Victor and Varki, Ajit and Areschoug, Thomas}},
issn = {{1083-351X}},
language = {{eng}},
number = {{39}},
pages = {{33981--33991}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{Human Siglec-5 Inhibitory Receptor and Immunoglobulin A (IgA) Have Separate Binding Sites in Streptococcal {beta} Protein.}},
url = {{http://dx.doi.org/10.1074/jbc.M111.251728}},
doi = {{10.1074/jbc.M111.251728}},
volume = {{286}},
year = {{2011}},
}