The invasin D protein fromYersinia pseudotuberculosisselectively binds the Fab region of host antibodies and affects colonization of the intestine.

2.50
Hdl Handle:
http://hdl.handle.net/10033/621332
Title:
The invasin D protein fromYersinia pseudotuberculosisselectively binds the Fab region of host antibodies and affects colonization of the intestine.
Authors:
Sadana, Pooja; Geyer, Rebecca; Pezoldt, Joern; Helmsing, Saskia; Huehn, Jochen ( 0000-0001-8071-1379 ) ; Hust, Michael; Dersch, Petra ( 0000-0001-8177-3280 ) ; Scrima, Andrea
Abstract:
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.
Affiliation:
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
The invasin D protein fromYersinia pseudotuberculosisselectively binds the Fab region of host antibodies and affects colonization of the intestine. 2018 J. Biol. Chem.
Journal:
The Journal of biological chemistry
Issue Date:
13-Mar-2018
URI:
http://hdl.handle.net/10033/621332
DOI:
10.1074/jbc.RA117.001068
PubMed ID:
29535184
Type:
Article
Language:
en
ISSN:
1083-351X
Appears in Collections:
publications of the NG Structurbiologie der Autophagie (SBAU); publications of the division experimentelle Immunologie (EXIM); publications of the department of molecular Infectionbiology (MIBI)

Full metadata record

DC FieldValue Language
dc.contributor.authorSadana, Poojaen
dc.contributor.authorGeyer, Rebeccaen
dc.contributor.authorPezoldt, Joernen
dc.contributor.authorHelmsing, Saskiaen
dc.contributor.authorHuehn, Jochenen
dc.contributor.authorHust, Michaelen
dc.contributor.authorDersch, Petraen
dc.contributor.authorScrima, Andreaen
dc.date.accessioned2018-03-23T15:04:02Z-
dc.date.available2018-03-23T15:04:02Z-
dc.date.issued2018-03-13-
dc.identifier.citationThe invasin D protein fromYersinia pseudotuberculosisselectively binds the Fab region of host antibodies and affects colonization of the intestine. 2018 J. Biol. Chem.en
dc.identifier.issn1083-351X-
dc.identifier.pmid29535184-
dc.identifier.doi10.1074/jbc.RA117.001068-
dc.identifier.urihttp://hdl.handle.net/10033/621332-
dc.description.abstractYersinia 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.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleThe invasin D protein fromYersinia pseudotuberculosisselectively binds the Fab region of host antibodies and affects colonization of the intestine.en
dc.typeArticleen
dc.contributor.departmentHelmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalThe Journal of biological chemistryen
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