Molecular dissection of protein-protein interactions between integrin alpha 5 beta 1 and the Helicobacter pylori Cag type IV secretion system

Kölblen, Thomas; Berge, Celia; Cherrier, Mickael V.; Brillet, Karl; Jimenez-Soto, Luisa; Ballut, Lionel; Takagi, Junichi; Montserret, Roland; Rousselle, Patricia; Fischer, Wolfgang; Haas, Rainer; Fronzes, Remi und Terradot, Laurent (2017): Molecular dissection of protein-protein interactions between integrin alpha 5 beta 1 and the Helicobacter pylori Cag type IV secretion system. In: Febs Journal, Bd. 284, Nr. 23: S. 4143-4157

Abstract

The more severe strains of the bacterial human pathogen Helicobacter pylori produce a type IV secretion system (cagT4SS) to inject the oncoprotein cytotoxin-associated gene A (CagA) into gastric cells. This syringe-like molecular apparatus is prolonged by an external pilus that exploits integrins as receptors to mediate the injection of CagA. The molecular determinants of the interaction of the cagT4SS pilus with the integrin ectodomain are still poorly understood. In this study, we have used surface plasmon resonance (SPR) to generate a comprehensive analysis of the protein-protein interactions between purified CagA, CagL, CagI, CagY repeat domain II (CagY(RRII)), CagY C-terminal domain (CagY(B10)) and integrin 51 ectodomain (51(E)) or headpiece domain (51(HP)). We found that CagI, CagA, CagL and CagY(B10) but not CagY(RRII) were able to interact with 51(E) with affinities similar to the one observed for 51(E) interaction with its physiological ligand fibronectin. We further showed that integrin activation and its associated conformational change increased CagA, CagL and CagY(B10) affinities for the receptor. Furthermore, CagI did not interact with integrin unless the receptor was in open conformation. CagI, CagA but not CagL and CagY(B10) interacted with the 51(HP). Our SPR study also revealed novel interactions between CagA and CagL, CagA and CagY(B10), and CagA and CagI. Altogether, our data map the network of interactions between host-cell 51 integrin and the cagT4SS proteins and suggest that activation of the receptor promotes interactions with the secretion apparatus and possibly CagA injection.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1742-464X
• Sprache: Englisch