Design and Structure Determination of a Composite Zinc Finger Containing a Nonpeptide Foldamer Helical Domain
dc.rights.license | open | en_US |
dc.relation.isnodouble | 3cb59348-1691-451e-9167-4be2b06706c6 | * |
hal.structure.identifier | Chimie et Biologie des Membranes et des Nanoobjets [CBMN] | |
dc.contributor.author | LOMBARDO, Caterina Maria | |
hal.structure.identifier | ARN : régulations naturelle et artificielle | |
dc.contributor.author | KUMAR, Vasantha M. V. | |
hal.structure.identifier | Chimie et Biologie des Membranes et des Nanoobjets [CBMN] | |
dc.contributor.author | DOUAT, Celine | |
hal.structure.identifier | Institut Européen de Chimie et de Biologie | |
dc.contributor.author | ROSU, Frederic | |
hal.structure.identifier | ARN : régulations naturelle et artificielle | |
dc.contributor.author | MERGNY, Jean-Louis | |
hal.structure.identifier | ARN : régulations naturelle et artificielle | |
dc.contributor.author | SALGADO, Gilmar F. | |
hal.structure.identifier | Chimie et Biologie des Membranes et des Nanoobjets [CBMN] | |
dc.contributor.author | GUICHARD, Gilles
IDREF: 084339268 | |
dc.date.accessioned | 2020-05-12T14:24:55Z | |
dc.date.available | 2020-05-12T14:24:55Z | |
dc.date.issued | 2019 | |
dc.identifier.issn | 0002-7863 | en_US |
dc.identifier.other | https://pubs.acs.org/doi/abs/10.1021/jacs.8b12240#notes1 | en_US |
dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/7554 | |
dc.description.abstractEn | A number of foldamer backbones have been described as useful mimics of protein secondary structure elements, enabling for example the design of synthetic oligomers with the ability to engage specific protein surfaces. Synthetic folded backbones can also be used to create artificial proteins in which a folded peptide segment (e.g., an alpha-helix, a loop) is replaced by its unnatural counterpart, with the expectation that the resulting molecule would maintain its ability to fold while manifesting new exploitable features. The similarities in screw sense, pitch, and polarity between peptide alpha-helices and oligourea 2.5-helices suggest that a tertiary structure could be retained when swapping the two backbones in a protein sequence. In the present work, we move a step toward the creation of such composite proteins by replacing the 10-residue long original alpha-helical segment in the Cys2His2 zinc finger 3 of transcription factor Egrl (also known as Zif268) by an oligourea sequence bearing two appropriately spaced imidazole side chains for zinc coordination. We show by spectroscopic techniques and mass spectrometry analysis under native conditions that the ability of the peptide/oligourea hybrid to coordinate the zinc ion is not affected by the foldamer replacement. Moreover, detailed NMR analysis provides evidence that the engineered zinc finger motif adopts a folded structure in which the native beta-sheet arrangement of the peptide region and global arrangement of DNA-binding side chains are preserved. Titration in the presence of the Egrl target DNA sequence supports binding to GC bases as reported for the wild type zinc finger. | |
dc.language.iso | EN | en_US |
dc.subject.en | Zinc | |
dc.subject.en | Peptides and proteins | |
dc.subject.en | Metals | |
dc.subject.en | Urea | |
dc.subject.en | Nuclear magnetic resonance spectroscopy | |
dc.title.en | Design and Structure Determination of a Composite Zinc Finger Containing a Nonpeptide Foldamer Helical Domain | |
dc.title.alternative | J. Am. Chem. Soc. | en_US |
dc.type | Article de revue | en_US |
dc.identifier.doi | 10.1021/jacs.8b12240 | |
dc.subject.hal | Chimie/Matériaux | en_US |
bordeaux.journal | Journal of the American Chemical Society | en_US |
bordeaux.page | 2516-2525 | en_US |
bordeaux.volume | 141 | en_US |
bordeaux.hal.laboratories | Institut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN) - UMR 5248 | en_US |
bordeaux.issue | 6 | 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-03184027 | |
hal.version | 1 | |
hal.date.transferred | 2021-03-29T08:48:25Z | |
hal.export | true | |
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