Structural insights into the AapA1 toxin of Helicobacter pylori
| dc.rights.license | open | en_US |
| hal.structure.identifier | Institut Européen de Chimie et Biologie [IECB] | |
| hal.structure.identifier | Régulations Naturelles et Artificielles [ARNA] | |
| dc.contributor.author | KORKUT, Dursun Nizam | |
| hal.structure.identifier | Chimie et Biologie des Membranes et des Nanoobjets [CBMN] | |
| dc.contributor.author | ALVES, Isabel | |
| dc.contributor.author | VOGEL, Alexander | |
| hal.structure.identifier | Régulations Naturelles et Artificielles [ARNA] | |
| dc.contributor.author | CHABAS, Sandrine | |
| dc.contributor.author | SHARMA, Cynthia M. | |
| hal.structure.identifier | Chimie et Biologie des Membranes et des Nanoobjets [CBMN] | |
| dc.contributor.author | MARTINEZ, Denis | |
| hal.structure.identifier | Chimie et Biologie des Membranes et des Nanoobjets [CBMN] | |
| dc.contributor.author | LOQUET, Antoine | |
| hal.structure.identifier | Institut Européen de Chimie et Biologie [IECB] | |
| hal.structure.identifier | Régulations Naturelles et Artificielles [ARNA] | |
| dc.contributor.author | SALGADO, Gilmar F. | |
| hal.structure.identifier | Régulations Naturelles et Artificielles [ARNA] | |
| dc.contributor.author | DARFEUILLE, Fabien | |
| dc.date.accessioned | 2020-05-13T14:15:24Z | |
| dc.date.available | 2020-05-13T14:15:24Z | |
| dc.date.issued | 2019 | |
| dc.identifier.issn | 0304-4165 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/7566 | |
| dc.description.abstractEn | BACKGROUND: We previously reported the identification of the aapA1/IsoA1 locus as part of a new family of toxin-antitoxin (TA) systems in the human pathogen Helicobacter pylori. AapA1 belongs to type I TA bacterial toxins, and both its mechanism of action towards the membrane and toxicity features are still unclear. METHODS: The biochemical characterization of the AapA1 toxic peptide was carried out using plasmid-borne expression and mutational approaches to follow its toxicity and localization. Biophysical properties of the AapA1 interaction with lipid membranes were studied by solution and solid-state NMR spectroscopy, plasmon waveguide resonance (PWR) and molecular modeling. RESULTS: We show that despite a low hydrophobic index, this toxin has a nanomolar affinity to the prokaryotic membrane. NMR spectroscopy reveals that the AapA1 toxin is structurally organized into three distinct domains: a positively charged disordered N-terminal domain (D), a single alpha-helix (H), and a basic C-terminal domain (R). The R domain interacts and destabilizes the membrane, while the H domain adopts a transmembrane conformation. These results were confirmed by alanine scanning of the minimal sequence required for toxicity. CONCLUSION: Our results have shown that specific amino acid residues along the H domain, as well as the R domain, are essential for the toxicity of the AapA1 toxin. GENERAL SIGNIFICANCE: Untangling and understanding the mechanism of action of small membrane-targeting toxins are difficult, but nevertheless contributes to a promising search and development of new antimicrobial drugs. | |
| dc.description.sponsorship | Rôle des systèmes toxine antitoxine de type I dans la persistence bactérienne - ANR-12-BSV5-0025 | en_US |
| dc.language.iso | EN | en_US |
| dc.subject.en | bacterial toxin | |
| dc.subject.en | toxin-antitoxin | |
| dc.subject.en | Helicobacter pylori | |
| dc.subject.en | transmembrane domain | |
| dc.subject.en | small membrane protein | |
| dc.title.en | Structural insights into the AapA1 toxin of Helicobacter pylori | |
| dc.title.alternative | bbagen | en_US |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1016/j.bbagen.2019.129423 | |
| dc.subject.hal | Chimie/Matériaux | en_US |
| bordeaux.journal | Biochimica et Biophysica Acta (BBA) - General Subjects | en_US |
| bordeaux.page | 129423-129423 | en_US |
| bordeaux.volume | 1864 | en_US |
| bordeaux.hal.laboratories | Institut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN) - UMR 5248 | en_US |
| bordeaux.issue | 1 | en_US |
| bordeaux.institution | Bordeaux INP | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| hal.identifier | hal-03182187 | |
| hal.version | 1 | |
| hal.date.transferred | 2021-03-26T09:59:10Z | |
| hal.export | true | |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Biochimica%20et%20Biophysica%20Acta%20(BBA)%20-%20General%20Subjects&rft.date=2019&rft.volume=1864&rft.issue=1&rft.spage=129423-129423&rft.epage=129423-129423&rft.eissn=0304-4165&rft.issn=0304-4165&rft.au=KORKUT,%20Dursun%20Nizam&ALVES,%20Isabel&VOGEL,%20Alexander&CHABAS,%20Sandrine&SHARMA,%20Cynthia%20M.&rft.genre=article |
Fichier(s) constituant ce document
| Fichiers | Taille | Format | Vue |
|---|---|---|---|
|
Il n'y a pas de fichiers associés à ce document. |
|||