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The invasin D protein from Yersinia pseudotuberculosis selectively binds the Fab region of host antibodies and affects colonization of the intestine
Open accessAbstract
Yersinia pseudotuberculosis is a Gram-negative bacterium and zoonotic pathogen responsible for a wide range of diseases, ranging from mild diarrhea, enterocolitis, lymphatic adenitis to persistent local inflammation.The Y. pseudotuberculosis invasin D (InvD) molecule belongs to the invasin (InvA)-type autotransporter proteins, but its structure and function remain unknown.In this study, we present the first crystal structure of InvD, analyzed its expression and function in a murine infection model, and identified its target molecule in the host.We found that InvD is induced at 37 °C and expressed in vivo 2-4 days after infection, indicating that InvD is a virulence factor.During infection, InvD was expressed in all parts of the intestinal tract, but not in deeper lymphoid tissues.The crystal structure of the C-terminal adhesion domain of InvD revealed a distinct Ig-related fold that, apart from the canonical -sheets, comprises various modifications of and insertions into the Ig-core structure.We identified the Fab fragment of host-derived IgG/IgA antibodies as the target of the adhesion domain.Phage display panning and flow cytometry data further revealed that InvD exhibits a preferential binding specificity toward antibodies with VH3/VK1 variable domains and that it is specifically recruited to a subset of B cells.This finding suggests that InvD modulates Ig functions in the intestine and affects direct interactions with a subset of cell surface-exposed B-cell receptors.In summary, our results provide extensive insights into the structure of InvD and its specific interaction with the target molecule in the host.
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Metadata
- Authors
- Sadana, P., Geyer, R., Pezoldt, J., Helmsing, S., Huehn, J., Hust, M., Dersch, P., & Scrima, A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 293
- Issue
- 22
- Pages
- 8672-8690
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2790556376
- Cited by
- 720
- References
- 83
- FWCI
- 45.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- creativecommons.org/licenses/by/4.0/ (vor, 817 d)
- Funders
- Helmholtz Association (VH-NG-727, VH-GS-202)
- Consortium for Functional Glycomics (GM62116, GM098791)
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- Sadana, P., Geyer, R., Pezoldt, J., Helmsing, S., Huehn, J., Hust, M., Dersch, P., & Scrima, A. (2018). The invasin D protein from Yersinia pseudotuberculosis selectively binds the Fab region of host antibodies and affects colonization of the intestine. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.ra117.001068
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