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The binding mechani...
The binding mechanism of the virulence factor Streptococcus suis adhesin P subtype to globotetraosylceramide is associated with systemic disease
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- Madar Johansson, Miralda (author)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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- Belurier, E. (author)
- University of Turku
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- Papageorgiou, A. C. (author)
- University of Turku,Åbo Akademi University
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- Sundin, Anders P. (author)
- Lund University,Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Rahkila, J. (author)
- Åbo Akademi University
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- Kallonen, T. (author)
- Turku University Hospital,Wellcome Trust Sanger Institute,University of Oslo,Åbo Akademi University
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- Nilsson, Ulf J. (author)
- Lund University,Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Maatsola, S. (author)
- University of Turku
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Nyholm, T. K. M. (author)
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- Kapyla, J. (author)
- University of Turku
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- Corander, J. (author)
- University of Helsinki,University of Oslo,Wellcome Trust Sanger Institute
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- Leino, R. (author)
- Åbo Akademi University
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- Finne, J. (author)
- University of Helsinki
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- Teneberg, Susann, 1955 (author)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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- Haataja, S. (author)
- University of Turku
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(creator_code:org_t)
- 2020
- 2020
- English.
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In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 295:42, s. 14305-14324
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http://dx.doi.org/10...
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Abstract
Subject headings
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- Streptococcus suis is part of the pig commensal microbiome but strains can also be pathogenic, causing pneumonia and meningitis in pigs as well as zoonotic meningitis. According to genomic analysis, S. suis is divided into asymptomatic carriage, respiratory and systemic strains with distinct genomic signatures. Because the strategies to target pathogenic S. suis are limited, new therapeutic approaches are needed. The virulence factor S. suis adhesin P (SadP) recognizes the galabiose Gal alpha 1-4Gal-oligosaccharide. Based on its oligosaccharide fine specificity, SadP can be divided into subtypes P-N and P-O. We show here that subtype P-N is distributed in the systemic strains causing meningitis, whereas type P-O is found in asymptomatic carriage and respiratory strains. Both types of SadP are shown to predominantly bind to pig lung globotriaosylceramide (Gb3). However, SadP adhesin from systemic subtype P-N strains also binds to globotetraosylceramide (Gb4). Mutagenesis studies of the galabiose-binding domain of type P-N SadP adhesin showed that the amino acid asparagine 285, which is replaced by an aspartate residue in type P-O SadP, was required for binding to Gb4 and, strikingly, was also required for interaction with the glycomimetic inhibitor phenylurea-galabiose. Molecular dynamics simulations provided insight into the role of Asn-285 for Gb4 and phenylurea-galabiose binding, suggesting additional hydrogen bonding to terminal GalNAc of Gb4 and the urea group. Thus, the Asn-285-mediated molecular mechanism of type P-N SadP binding to Gb4 could be used to selectively target S. suis in systemic disease without interfering with commensal strains, opening up new avenues for interventional strategies against this pathogen.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- glycolipid
- adhesin
- cell surface receptor
- ligand-binding protein
- glycobiology
- globotetraosylceramide
- globotriaosylceramide
- Gb3
- Gb4
- SadP
- globotetraosylceramide
- bacterial adhesion
- mass-spectrometry
- protein
- glycolipids
- glycans
- ions
- coli
- sadp
- Biochemistry & Molecular Biology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Madar Johansson, ...
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Belurier, E.
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Papageorgiou, A. ...
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Sundin, Anders P ...
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Rahkila, J.
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Kallonen, T.
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show more...
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Nilsson, Ulf J.
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Maatsola, S.
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Nyholm, T. K. M.
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Kapyla, J.
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Corander, J.
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Leino, R.
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Finne, J.
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Teneberg, Susann ...
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Haataja, S.
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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Journal of Biolo ...
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University of Gothenburg
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Lund University