| dc.rights.license | open | en_US |
| hal.structure.identifier | Microbiologie moléculaire et biochimie structurale - Molecular Microbiology and Structural Biochemistry [MMSB] | |
| dc.contributor.author | BLANC, Marine | |
| hal.structure.identifier | Max Von Pettenkofer Institute [MVP] | |
| dc.contributor.author | LETTL, Clara | |
| hal.structure.identifier | Microbiologie moléculaire et biochimie structurale - Molecular Microbiology and Structural Biochemistry [MMSB] | |
| dc.contributor.author | GUERIN, Jeremy | |
| hal.structure.identifier | Microbiologie moléculaire et biochimie structurale - Molecular Microbiology and Structural Biochemistry [MMSB] | |
| dc.contributor.author | VIEILLE, Anaïs | |
| hal.structure.identifier | Universität Zürich [Zürich] = University of Zurich [UZH] | |
| dc.contributor.author | FURLER, Sven | |
| hal.structure.identifier | Universität Zürich [Zürich] = University of Zurich [UZH] | |
| dc.contributor.author | BRIAND-SCHUMACHER, Sylvie | |
| hal.structure.identifier | Universität Zürich [Zürich] = University of Zurich [UZH] | |
| dc.contributor.author | DREIER, Birgit | |
| hal.structure.identifier | Microbiologie moléculaire et biochimie structurale - Molecular Microbiology and Structural Biochemistry [MMSB] | |
| dc.contributor.author | BERGE, Celia | |
| hal.structure.identifier | Universität Zürich [Zürich] = University of Zurich [UZH] | |
| dc.contributor.author | PLÜCKTHUN, Andreas | |
| hal.structure.identifier | Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 [LBTI] | |
| dc.contributor.author | VADON-LE GOFF, Sandrine | |
| hal.structure.identifier | Microbiologie Fondamentale et Pathogénicité [MFP] | |
| dc.contributor.author | FRONZES, Remi | |
| hal.structure.identifier | Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 [LBTI] | |
| dc.contributor.author | ROUSSELLE, Patricia | |
| hal.structure.identifier | Max Von Pettenkofer Institute [MVP] | |
| dc.contributor.author | FISCHER, Wolfgang | |
| hal.structure.identifier | Microbiologie moléculaire et biochimie structurale - Molecular Microbiology and Structural Biochemistry [MMSB] | |
| dc.contributor.author | TERRADOT, Laurent | |
| dc.date.accessioned | 2024-04-24T09:25:23Z | |
| dc.date.available | 2024-04-24T09:25:23Z | |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/199298 | |
| dc.description.abstractEn | The bacterial human pathogen Helicobacter pylori produces a type IV secretion system ( cag T4SS) to inject the oncoprotein CagA into gastric cells. The cag T4SS external pilus mediates attachment of the apparatus to the target cell and the delivery of CagA. While the composition of the pilus is unclear, CagI is present at the surface of the bacterium and required for pilus formation. Here, we have investigated the properties of CagI by an integrative structural biology approach. Using Alpha Fold 2 and Small Angle X-ray scattering, it was found that CagI forms elongated dimers mediated by rod-shape N-terminal domains (CagI N ) prolonged by globular C-terminal domains (CagI C ). Three Designed Ankyrin Repeat Proteins (DARPins) K2, K5 and K8 selected against CagI interacted with CagI C with subnanomolar affinities. The crystal structures of the CagI:K2 and CagI:K5 complexes were solved and identified the interfaces between the molecules, thereby providing a structural explanation for the difference in affinity between the two binders. Purified CagI and CagI C were found to interact with adenocarcinoma gastric (AGS) cells, induced cell spreading and the interaction was inhibited by K2. The same DARPin inhibited CagA translocation by up to 65% in AGS cells while inhibition levels were 40% and 30% with K8 and K5, respectively. Our study suggests that CagI C plays a key role in cag T4SS-mediated CagA translocation and that DARPins targeting CagI represent potent inhibitors of the cag T4SS, a crucial risk factor for gastric cancer development. | |
| dc.description.sponsorship | Bases structurale du système de secretion de type IV d'Helicobacter pylori | en_US |
| dc.description.sponsorship | Bases structurales et moléculaires de l'exploitation de l'integrin a5ß1 par le système de sécrétion de type IV d'Helicobacter pylori - ANR-13-ISV3-0006 | en_US |
| dc.language.iso | EN | en_US |
| dc.rights | Attribution-NonCommercial 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc/3.0/us/ | * |
| dc.title.en | Designed Ankyrin Repeat Proteins provide insights into the structure and function of CagI and are potent inhibitors of CagA translocation by the Helicobacter pylori type IV secretion system | |
| dc.type | Document de travail - Pré-publication | en_US |
| dc.identifier.doi | 10.1101/2022.11.08.515452 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Microbiologie et Parasitologie/Bactériologie | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biologie structurale [q-bio.BM] | en_US |
| bordeaux.journal | PLoS Pathogens | en_US |
| bordeaux.hal.laboratories | MFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234 | en_US |
| bordeaux.institution | CNRS | en_US |
| bordeaux.import.source | hal | |
| hal.identifier | hal-04246055 | |
| hal.version | 1 | |
| hal.popular | non | en_US |
| hal.audience | Internationale | en_US |
| hal.export | false | |
| workflow.import.source | hal | |
| dc.rights.cc | Pas de Licence CC | en_US |
| bordeaux.subtype | Prepublication/Preprint | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=PLoS%20Pathogens&rft.au=BLANC,%20Marine&LETTL,%20Clara&GUERIN,%20Jeremy&VIEILLE,%20Ana%C3%AFs&FURLER,%20Sven&rft.genre=preprint | |
