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The invasin D protein fromYersinia pseudotuberculosisselectively binds the Fab region of host antibodies and affects colonization of the intestine.
Sadana, Pooja Geyer, Rebecca Pezoldt, Joern Helmsing, Saskia Hust, Michael Scrima, Andrea
Sadana, Pooja
Geyer, Rebecca
Pezoldt, Joern
Helmsing, Saskia
Hust, Michael
Scrima, Andrea
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2018-03-13
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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. TheY. pseudotuberculosisinvasin 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 vivo2-4 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 β-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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The invasin D protein fromYersinia pseudotuberculosisselectively binds the Fab region of host antibodies and affects colonization of the intestine. 2018 J. Biol. Chem.
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en
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1083-351X