The invasin D protein from Yersinia pseudotuberculosis selectively binds the Fab region of host antibodies and affects colonization of the intestine

• Published in: The Journal of biological chemistry Vol. 293; no. 22; pp. 8672 - 8690
• Main Authors: Sadana, Pooja, Geyer, Rebecca, Pezoldt, Joern, Helmsing, Saskia, Huehn, Jochen, Hust, Michael, Dersch, Petra, Scrima, Andrea
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2018; American Society for Biochemistry and Molecular Biology
• Subjects: adhesin; Adhesins, Bacterial - chemistry; Adhesins, Bacterial - metabolism; Amino Acid Sequence; Animals; Antibodies - immunology; Antibodies - metabolism; Bacterial Adhesion; Editors' Picks; Fab-binding; Female; Immunoglobulin Fab Fragments - immunology; Immunoglobulin Fab Fragments - metabolism; Intestines - immunology; Intestines - microbiology; Intestines - pathology; invasin; InvD; Mice; Mice, Inbred BALB C; Models, Molecular; phage display; protein chemistry; Protein Conformation; Sequence Homology; small-angle X-ray scattering (SAXS); Virulence; X-ray crystallography; Yersinia pseudotuberculosis; Yersinia pseudotuberculosis - immunology; Yersinia pseudotuberculosis - pathogenicity; Yersinia pseudotuberculosis Infections - metabolism; Yersinia pseudotuberculosis Infections - microbiology; Yersinia pseudotuberculosis Infections - pathology; X-ray crystallography; InvD; adhesin; phage display; small-angle X-ray scattering (SAXS); invasin; protein chemistry; Fab-binding; Yersinia pseudotuberculosis
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.RA117.001068

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 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.